Researcher Database

Yasuhiro Kon
Faculty of Veterinary Medicine Veterinary Medicine Basic Veterinary Sciences
Professor

Researcher Profile and Settings

Affiliation

  • Faculty of Veterinary Medicine Veterinary Medicine Basic Veterinary Sciences

Job Title

  • Professor

J-Global ID

Research Interests

  • 不妊症   自己免疫疾患   精子形成   Urogenital organ   

Research Areas

  • Life sciences / Veterinary medicine
  • Life sciences / Veterinary medicine
  • Life sciences / Veterinary medicine

Academic & Professional Experience

  • 2017/04 - Today 北海道大学 大学院獣医学研究院 教授
  • 2003/04 - 2017/03 Hokkaido University Graduate School of Veterinary Medicine Professor
  • 1994/10 - 2003/03 Hokkaido University Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine Associate Professor
  • 1984/11 - 1994/09 Hokkaido University Faculty of Veterinary Medicine Instructor (Assistant Professor)

Education

  • 1983/04 - 1984/11  Hokkaido University  Graduate School of Veterinary Medicine  Doctor Course
  • 1981/04 - 1983/03  Hokkaido University  Graduate School of Veterinary Medicine  Master Course
  • 1977/04 - 1981/03  Hokkaido University  Faculty of Veterinary Medicine

Association Memberships

  • Japanese Association of Veterinary Nephrology and Urology   THE JAPANESE ASSOCIATION OF ANATOMISTS   日本繁殖生物学会   JAPANESE SOCIETY OF VETERINARY SCIENCE   

Research Activities

Published Papers

  • An experimental study of menopause induced by bilateral ovariectomy and mechanistic effects of mesenchymal stromal cell therapy on the parotid gland of a rat model.
    El-Naseery NI, Elewa YHA, Ichii O, Kon Y
    Ann Anat 220 9 - 20 2018/11 [Refereed][Not invited]
  • Restricted localization of ultimobranchial body remnants and parafollicular cells in the one-humped camel (Camelus dromedarius).
    Nakamura T, Elewa YHA, Ichii O, Hosotani M, Ghonimi WAM, Tatsumi O, Nagasaki KI, Kon Y
    J Vet Med Sci 80 (9) 1368 - 1372 2018/09 [Refereed][Not invited]
  • Abnormal Morphology of Distal Tubular Epithelial Cells Is Regulated by Genetic Factors Derived from Mouse Chromosome 12.
    Ichii O, Nakamura T, Horino T, Yabuki A, Elewa YHA, Kon Y
    Am J Pathol 188 (9) 2120 - 2138 2018/09 [Refereed][Not invited]
  • Cotton rat (Sigmodon hispidus) develops metabolic disorders associated with visceral adipose inflammation and fatty pancreas without obesity.
    Nakamura T, Ichii O, Irie T, Kouguchi H, Sotozaki K, Chihara M, Sunden Y, Nagasaki KI, Tatsumi O, Elewa YHA, Kon Y
    Cell Tissue Res 2018/08 [Refereed][Not invited]
  • Analysis for genetic loci controlling protoscolex development in the Echinococcus multilocularis infection using congenic mice.
    Islam MA, Torigoe D, Kameda Y, Irie T, Kouguchi H, Nakao R, Masum MA, Ichii O, Kon Y, Tag-El-Din-Hassan HT, Morimatsu M, Yagi K, Agui T
    Infect Genet Evol 65 65 - 71 2018/07 [Refereed][Not invited]
  • Modified scanning electron microscopy reveals pathological crosstalk between endothelial cells and podocytes in a murine model of membranoproliferative glomerulonephritis.
    Masum MA, Ichii O, Elewa YHA, Nakamura T, Otani Y, Hosotani M, Kon Y
    Sci Rep 8 (1) 10276  2018/07 [Refereed][Not invited]
  • Noreldin AE, Elewa YHA, Kon Y, Warita K, Hosaka YZ
    Acta Histochem 120 (4) 323 - 328 2018/05 [Refereed][Not invited]
  • Ovarian mast cells migrate toward ovary-fimbria connection in neonatal MRL/MpJ mice.
    Nakamura T, Chihara M, Ichii O, Otsuka-Kanazawa S, Nagasaki KI, Elewa YHA, Tatsumi O, Kon Y
    PLoS One 13 (4) e0196364  2018/04 [Refereed][Not invited]
  • Close pathological correlations between chronic kidney disease and reproductive organ-associated abnormalities in female cotton rats.
    Ichii O, Nakamura T, Irie T, Kouguchi H, Sotozaki K, Horino T, Sunden Y, Elewa YHA, Kon Y
    Exp Biol Med (Maywood). 243 (5) 418 - 427 2018/03 [Refereed][Not invited]
  • Histopathological Correlations between Mediastinal Fat-Associated Lymphoid Clusters and the Development of Lung Inflammation and Fibrosis following Bleomycin Administration in Mice.
    Elewa YHA, Ichii O, Takada K, Nakamura T, Masum MA, Kon Y
    Front Immunol. 9 271  2018/02 [Refereed][Not invited]
  • M. Hosotani, O. Ichii, T. Nakamura, S. O. Kanazawa, Y. Hosny Ali Elewa, Y. Kon
    LUPUS 27 (1) 82 - 94 0961-2033 2018/01 [Refereed][Not invited]
     
    Ovulation and oocyte-pick-up are essential processes in fertilization. Herein, we found associations between autoimmune disease and the aforementioned processes in mice. At three and six months, along with the evaluation of autoimmune disease indices, the ovary, mesosalpinx, and oviducts were histologically examined in C57BL/6, MRL/MpJ, and MRL/MpJ-Fas(lpr/lpr) mice as healthy control, mild and severe models of autoimmune disease, respectively. In superovulated mice, the number of oocyte cumulus complexes found in the ampulla was macroscopically counted, and that of ovulated oocytes was histologically evaluated, as indicated by ruptured follicles or corpora hemorrhagica in ovaries. Finally, the oocyte-pick-up rate was calculated. In MRL/MpJ-Fas(lpr/lpr) mice, the oocyte-pick-up rate decreased with disease-related deterioration, unlike in other mouse strains. Further, more ovulated oocytes were found in MRL/MpJ mice than in C57BL/6 mice, and this number significantly decreased with aging in MRL/MpJ-Fas(lpr/lpr) mice. Numerous T-cells infiltrated into the infundibulum or a part of the mesosalpinx in aged MRL/MpJ-Fas(lpr/lpr) mice, and their infundibulum showed swelling and fewer ciliated epithelial cells compared to that of C57BL/6 mice. In conclusion, the progression of severe autoimmune disease affected the oocyte-pick-up process through histopathological changes in the infundibulum. These results provide important insights into female infertility associated with autoimmune disease.
  • Cotton rats (Sigmodon hispidus) possess pharyngeal pouch remnants originating from different primordia
    Nakamura T, Ichii O, Irie T, Mizoguchi T, Shinohara A, Kouguchi H, Sunden Y, Otsuka-Kanazawa S, Elewa YH, Yoshimoto C, Nagasaki KI, Kon Y
    Histol Histopathol 11946  2017/11 [Refereed][Not invited]
  • Osamu Ichii, Junpei Kimura, Tadashi Okamura, Taro Horino, Teppei Nakamura, Hayato Sasaki, Yaser Hosny Ali Elewa, Yasuhiro Kon
    FRONTIERS IN IMMUNOLOGY 8 1346  1664-3224 2017/10 [Refereed][Not invited]
     
    IL-36 alpha, a member of the IL-1 family, is a crucial mediator of inflammatory responses. We previously found that IL-36 alpha was overexpressed in injured distal tubules (DTs); however, its pathological function remains unclear. Herein, unilateral ureter obstruction (UUO) or folic acid (FA) injection was performed in mouse kidneys to assess the role of IL-36 alpha in kidney injury. IL-36 alpha mRNA and protein expression significantly increased in the kidneys within 24 h after UUO. IL-36 alpha localized to dilated DTs. IL-36 alpha expression significantly correlated with the progression of tubulointerstitial cell infiltration and tubular epithelium cell death in UUO kidneys and with renal dysfunction in FA-induced acute kidney injury mice. At 24 h after UUO, IL-36 alpha(+) DT epithelial cells showed loose intercellular digitations. IL-1RL2, an IL-36 alpha receptor protein, localized to podocytes, proximal tubules, and DTs in the healthy kidney. IL-1RL2 was expressed in interstitial cells and platelets or extended primary cilia of DT epithelial cells in UUO kidneys. IL-36 alpha stimulation promoted the production of IL-6 and Prss35, an inflammatory cytokine and collagen remodeling-associated enzyme, respectively, in cultured NIH3T3 fibroblasts. UUO-treated IL-36 alpha-knockout (KO) mice showed milder kidney injury features than wild-type (WT) mice did. In UUO kidneys from IL-36 alpha-KO mice, the expression of genes associated with inflammatory response and sensory perception was significantly different from that in WT mice. Altogether, our data indicate an association between intrarenal IL-36 alpha overexpression and the progression of tubulointerstitial inflammations and morpho-functional alterations of DT epithelial cells. IL-36 alpha may be a novel kidney injury marker useful for evaluating DT damages.
  • Local CD34-positive capillaries decrease in mouse models of kidney disease associating with the severity of glomerular and tubulointerstitial lesions
    Masum MA, Ichii O, Elewa YH, Nakamura T, Kon Y
    BMC Nephrol 18 (1) 280  2017/09 [Refereed][Not invited]
  • Teppei Nakamura, Naoya Karakida, Ai Dantsuka, Osamu Ichii, Yaser Hosny Ali Elewa, Yasuhiro Kon, Ken-ichi Nagasaki, Hideki Hattori, Tomoji Yoshiyasu
    JOURNAL OF VETERINARY MEDICAL SCIENCE 79 (7) 1230 - 1235 0916-7250 2017/07 [Refereed][Not invited]
     
    Syrian golden hamsters (Mesocricetus auratus) are useful laboratory rodents for studying human infectious diseases, metabolic diseases and cancer. In other rodents, such as mice and rats, a mixture of medetomidine, midazolam and butorphanol functions as a useful anesthetic, although it alters some blood biochemical parameters. In this study, we examined the effects of this mixture on anesthesia and blood biochemical parameters, and the action of atipamezole, a medetomidine antagonist, in hamsters. Intramuscular injection of a mixture of medetomidine, midazolam and butorphanol at doses of 0.15, 2.0 and 2.5 mg/kg, respectively, had a short induction time (within 5 min) and produced an anesthetic duration of approximately 100 min in hamsters. We also demonstrated that 0.15 mg/kg of atipamezole, corresponding to the same dose as medetomidine, made hamsters recover quickly from anesthesia. The anesthetic agent markedly altered metabolic parameters, such as plasma glucose and insulin; however, 0.15 mg/kg of atipamezole returned these levels to normal range within approximately 10 min after the injection. The anesthetic also slightly altered mineral levels, such as plasma inorganic phosphorus, calcium and sodium; the latter two were also improved by atipamezole. Our results indicated that the mixture of medetomidine, midazolam, and butorphanol at doses of 0.15, 2.0 and 2.5 mg/kg, respectively, functioned as an effective anesthetic, and atipamezole was useful for antagonizing both anesthesia and biochemical alteration in hamsters.
  • Analysis of the mechanism of radiation-induced upregulation of mitochondrial abundance in mouse fibroblasts
    Yamamori T, Sasagawa T, Ichii O, Miyoshi M, Bo T, Yasui H, Kon Y, Inanami O
    J Radiat Res 58 (3) 292 - 301 2017/05 [Refereed][Not invited]
  • Osamu Ichii, Masataka Chihara, Shin-Hyo Lee, Teppei Nakamura, Saori Otsuka-Kanazawa, Taro Horino, Yaser Hosny Ali Elewa, Yasuhiro Kon
    AUTOIMMUNITY 50 (2) 114 - 124 0891-6934 2017/03 [Refereed][Not invited]
     
    Inbred MRL/MpJ mice show several unique phenotypes in tissue regeneration processes and the urogenital and immune systems. Clarifying the genetic and molecular bases of these phenotypes requires the analysis of their genetic susceptibility locus. Herein, hydronephrosis development was incidentally observed in MRL/MpJ-derived chromosome 11 (D11Mit21-212)-carrying C57BL/6N-based congenic mice, which developed bilateral or unilateral hydronephrosis in both males and females with 23.5% and 12.5% prevalence, respectively. Histopathologically, papillary malformations of the transitional epithelium in the pelvic-ureteric junction seemed to constrict the ureter luminal entrance. Characteristically, eosinophilic crystals were observed in the lumen of diseased ureters. These ureters were surrounded by infiltrating cells mainly composed of numerous CD3(+)T-cells and B220(+)B-cells. Furthermore, several Iba-1(+)macrophages, Gr-1(+)granulocytes, mast cells and chitinase 3-like 3/Ym1 (an important inflammatory lectin)-positive cells were detected. Eosinophils also accumulated to these lesions in diseased ureters. Some B6.MRL-(D11Mit21-D11Mit212) mice had duplicated ureters. We determined>100 single nucleotide variants between C57BL/6N- and MRL/MpJ-type chromosome 11 congenic regions, which were associated with nonsynonymous substitution, frameshift or stopgain of coding proteins. In conclusion, B6.MRL-(D11Mit21-D11Mit212) mice spontaneously developed hydronephrosis due to obstructive uropathy with inflammation. Thus, this mouse line would be useful for molecular pathological analysis of obstructive uropathy in experimental medicine.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon
    AUTOIMMUNITY 50 (5) 306 - 316 0891-6934 2017 [Refereed][Not invited]
     
    MRL/MpJ-Fas(lpr) (lpr) mice are a model for autoimmune diseases such as systemic lupus erythematosus (SLE). These diseases mainly affect women, with a 10:1 female-to-male ratio, and cause pleuropulmonary lesions. We previously revealed a correlation between mediastinal fat-associated lymphoid cluster (MFALC) development and cellular infiltration in the lungs of lpr male mice; however, we did not report on MFALCs in females. The purpose of this investigation was to reveal sex-related differences in MFALCs in lpr mice. We compared the morphological features of MFALCs and lung mononuclear cell aggregates (LMCAs) in 5-month-old male and female lpr mice. The females showed significantly elevated anti-dsDNA autoantibody titers and larger MFALCs, with a higher ratio of lymphatic vessel (LV) and high endothelial venule (HEV) areas to MFALC area, and greater numbers of T- and B-cells, macrophages, and proliferating and dendritic cells in MFALCs and LMCAs than males. Our data indicated that MFALCs were more developed and lung lesions were more severe in female than in male lpr mice, thereby suggesting a potential role for LVs and HEVs in the establishment of MFALCs and lung lesions. Further investigation in female lpr mice will be needed for treatment of human respiratory diseases and autoimmune disorders.
  • Urinary exosome-derived microRNAs reflecting the changes of renal function and histopathology in dogs
    Ichii O, Ohta H, Torino T, Nakamura T, Hosotani M, Mizoguchi T, Morishita K, Nakamura K, Hoshino Y, Takagi S, Sasaki N, Takiguchi M, Sato R, Oyamada K, Kon Y
    Sci Rep 7 40340  2017/01 [Refereed][Not invited]
  • Teppei Ikeda, Osamu Ichii, Saori Otsuka-Kanazawa, Teppei Nakamura, Yaser Hosny Ali Elewa, Yasuhiro Kon
    JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY 37 (4-5) 153 - 164 0142-4319 2016/10 [Refereed][Not invited]
     
    Skeletal muscle myofibers constantly undergo degeneration and regeneration. Histopathological features of 6 skeletal muscles (cranial tibial [CT], gastrocnemius, quadriceps femoris, triceps brachii [TB], lumbar longissimus muscles, and costal part of the diaphragm [CPD]) were compared using C57BL/10ScSn-Dmd (mdx) (mdx) mice, a model for muscular dystrophy versus control, C57BL/10 mice. Body weight and skeletal muscle mass were lower in mdx mice than the control at 4 weeks of age; these results were similar at 6-30 weeks. Additionally, muscular lesions were observed in all examined skeletal muscles in mdx mice after 4 weeks, but none were noted in the controls. Immunohistochemical staining revealed numerous paired box 7-positive satellite cells surrounding the embryonic myosin heavy chain-positive regenerating myofibers, while the number of the former and staining intensity of the latter decreased as myofiber regeneration progressed. Persistent muscular lesions were observed in skeletal muscles of mdx mice between 4 and 14 weeks of age, and normal myofibers decreased with age. Number of muscular lesions was lowest in CPD at all ages examined, while the ratio of normal myofibers was lowest in TB at 6 weeks. In CT, TB, and CPD, Iba1-positive macrophages, the main inflammatory cells in skeletal muscle lesions, showed a significant positive correlation with the appearance of regenerating myofibers. Additionally, B220-positive B-cells showed positive and negative correlation with regenerating and regenerated myofibers, respectively. Our data suggest that degenerative and regenerative features of myofibers differ among skeletal muscles and that inflammatory cells are strongly associated with regenerative features of myofibers in mdx mice.
  • Dugar Delgermurun, Soichiro Yamaguchi, Osamu Ichii, Yasuhiro Kon, Shigeo Ito, Ken-ichi Otsuguro
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 187 43 - 49 1532-0456 2016/09 [Refereed][Not invited]
     
    Epithelioid cells in the chicken thoracic aorta are chemoreceptor cells that release 5-HT in response to hypoxia. It is likely that these cells play a role in chemoreception similar to that of glomus cells in the carotid bodies of mammals. Recently, H2S was reported to be a key mediator of carotid glomus cell responses to hypoxia. The aim of the present study was to reveal the mechanism of action of H2S on 5-HT outflow from chemoreceptor cells in the chicken thoracic aorta. The 5-HT outflow induced by NaHS, an H2S donor, and Na2S3, a polysulfide, was measured by using a HPLC equipped with an electrochemical detector. NaHS (0.3-3 mM) caused a concentration-dependent increase in 5-HT outflow, which was significantly inhibited by the removal of extracellular Ca2+. outflow induced by NaHS (0.3 mM) was also significantly inhibited by voltage-dependent L- and N-type Ca2+ channel blockers and a selective TRPA1 channel blocker. Cinnamaldehyde, a TRPA1 agonist, mimicked the secretory response to H2S. 5-HT outflow induced by Na2S3 (10 M) was also inhibited by the TRPA1 channel blocker. Furthermore, the expression of TRPA1 was localized to 5-HT-containing chemoreceptor cells in the aortic wall. These findings suggest that the activation of TRPA1 and voltage-dependent Ca2+ channels is involved in H2S-evoked 5-HT release from chemoreceptor cells in the chicken aorta. (C) 2016 Elsevier Inc. All rights reserved.
  • Osamu Ichii, Teppei Nakamura, Takao Irie, Hirokazu Kouguchi, Daisuke Nakamura, Saori Nakamura, Shinobu Sato, Keisuke Yokoyama, Taro Horino, Yuji Sunden, Yaser Hosny Ali Elewa, Yasuhiro Kon
    HISTOCHEMISTRY AND CELL BIOLOGY 146 (3) 351 - 362 0948-6143 2016/09 [Refereed][Not invited]
     
    The cotton rat (Sigmodon hispidus) is a laboratory rodent that has been used for studies on human infectious diseases. In the present study, we observed that female cotton rats, not the male cotton rats, developed chronic anemia characterized by reduced red blood cell, hemoglobin, and hematocrit levels from 5 to 9 months of age without any changes in the mean corpuscular hemoglobin and volume levels. In peripheral blood, the reticulocyte count did not increase in response to anemia in female cotton rats, and no extramedullary hematopoiesis was observed in the liver or spleen. Further, the serum levels of urea nitrogen and creatinine increased from 5 to 9 months of age in female cotton rats compared to male cotton rats, and these increases became more prominent from 10 months of age onward, indicating chronic kidney disease. Histopathologically, female cotton rats manifested tubulointerstitial lesions characterized by the infiltration of mononuclear cells, including plasma cells and CD3(+) T-cells, as well as the dilation of calbindin-D28k(+) distal tubules from 5 to 9 months of age. The severity of these lesions progressed from 10 months of age onward, and renal fibrotic features and numerous tubular cysts appeared without any obvious glomerular lesions. A significant decrease in the erythropoietin protein levels was observed in the kidney of aged female cotton rats, and significant correlations were detected between anemia and tubulointerstitial damage. These results suggest that aged female cotton rats chronically develop renal anemia, and this rodent may serve as a novel model to elucidate its pathogenesis.
  • Truc Quynh Thai, Huy Bang Nguyen, Sei Saitoh, Bao Wu, Yurika Saitoh, Satoshi Shimo, Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon, Takashi Takaki, Kensuke Joh, Nobuhiko Ohno
    MEDICAL MOLECULAR MORPHOLOGY 49 (3) 154 - 162 1860-1480 2016/09 [Refereed][Not invited]
     
    Serial block-face imaging using scanning electron microscopy enables rapid observations of three-dimensional ultrastructures in a large volume of biological specimens. However, such imaging usually requires days for sample preparation to reduce charging and increase image contrast. In this study, we report a rapid procedure to acquire serial electron microscopic images within 1 day for three-dimensional analyses of subcellular ultrastructures. This procedure is based on serial block-face with two major modifications, including a new sample treatment device and direct polymerization on the rivets, to reduce the time and workload needed. The modified procedure without uranyl acetate can produce tens of embedded samples observable under serial block-face scanning electron microscopy within 1 day. The serial images obtained are similar to the block-face images acquired by common procedures, and are applicable to three-dimensional reconstructions at a subcellular resolution. Using this approach, regional immune deposits and the double contour or heterogeneous thinning of basement membranes were observed in the glomerular capillary loops of an autoimmune nephropathy model. These modifications provide options to improve the throughput of three-dimensional electron microscopic examinations, and will ultimately be beneficial for the wider application of volume imaging in life science and clinical medicine.
  • Sawa Onouchi, Osamu Ichii, Teppei Nakamura, Yaser Hosny Ali Elewa, Yasuhiro Kon
    CELL AND TISSUE RESEARCH 365 (2) 367 - 379 0302-766X 2016/08 [Refereed][Not invited]
     
    Although gut flexures characterize gut morphology, the mechanisms underlying flexure formation remain obscure. Previously, we analyzed the mouse duodenojejunal flexure (DJF) as a model for its formation and reported asymmetric morphologies between the inner and outer bending sides of the fetal mouse DJF, implying their contribution to DJF formation. We now present the extracellular matrix (ECM) as an important factor for gut morphogenesis. We investigate ECM distribution during mouse DJF formation by histological techniques. In the intercellular space of the gut wall, high Alcian-Blue positivity for proteoglycans shifted from the outer to the inner side of the gut wall during DJF formation. Immunopositivity for fibronectin, collagen I, or pan-tenascin was higher at the inner than at the outer side. Collagen IV and laminins localized to the epithelial basement membrane. Beneath the mesothelium at the pre-formation stage, collagen IV and laminin immunopositivity showed inverse results, corresponding to the different cellular characteristics at this site. At the post-formation stage, however, laminin positivity beneath the mesothelium was the reverse of that observed during the pre-formation stage. High immunopositivity for collagen IV and laminins at the inner gut wall mesenchyme of the post-formation DJF implied a different blood vessel distribution. We conclude that ECM distribution changes spatiotemporally during mouse DJF formation, indicating ECM association with the establishment of asymmetric morphologies during this process.
  • Daichi Shiozuru, Osamu Ichii, Junpei Kimura, Teppei Nakamura, Yaser Hosny Ali Elewa, Saori Otsuka-Kanazawa, Yasuhiro Kon
    HISTOLOGY AND HISTOPATHOLOGY 31 (2) 189 - 204 0213-3911 2016/02 [Refereed][Not invited]
     
    Clarification of the renal repair process is crucial for developing novel therapeutic strategies for kidney injury. MRL/MpJ mice have a unique repair process characterized by low scar formation. The pathological features of experimentally injured MRL/MpJ and C57BL/6 mouse kidneys were compared to examine the renal repair process. The dilation and atrophy of renal tubules were observed in folic acid (FA)-induced acute kidney injury (AKI) in both strains, and the histopathological injury scores and number of interleukin (IL)-1F6-positive damaged distal tubules and kidney injury molecule 1 (KIM-1)-positive damaged proximal tubules drastically increased 1 day after AKI induction. However, KIM-1-positive tubules and the elevation of serum renal function markers were significantly fewer and lower, respectively, in MRL/MpJ mice at days 2 and 7 after AKI. After traumatic kidney injury (TKI) via needle puncture, severe tubular necrotic lesions in the punctured area and fibrosis progressed in both strains. Indices for fibrosis such as aniline blue-positive area, number of alpha smooth muscle actin-positive myofibroblasts, and messenger RNA expression levels of Tgfb1 and Mmp2 indicated lower fibrotic activity in MRL/MpJ kidneys. Characteristically, only MRL/MpJ kidneys manifested remarkable calcification around the punctured area beginning 7 days after TKI. The pathological features of injured MRL/MpJ and C57BL/6 kidneys differed, especially those of kidneys with mild proximal tubular injuries after FA-induced AKI. Lower fibrotic activity and increased calcification after TKI were observed in MRL/MpJ kidneys. These findings clarified the unique pathological characteristics of MRL/MpJ mouse kidneys and contribute to understanding of the renal repair process after kidney injury.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon
    IMMUNOLOGY 147 (1) 30 - 40 0019-2805 2016/01 [Refereed][Not invited]
     
    We previously discovered mediastinal fat-associated lymphoid clusters (MFALCs) as novel lymphoid clusters associated with mediastinal fat tissue in healthy mice. However, no data about their morphology in immune-associated disease conditions, and their relationship with lung infiltration, is available to date. In the present study, we compared the morphological features of MFALCs in 4-month-old male murine autoimmune disease models (MRL/MpJ-lpr mice and BXSB/MpJ-Yaa mice) with those of the corresponding control strains (MRL/MpJ and BXSB/MpJ, respectively). In addition, we analysed their correlation with lung infiltration. Furthermore, immunohistochemistry for CD3, B220, Iba1, Gr1 and BrdU was performed to detect T cells and B cells, macrophages, granulocytes and proliferating cells, respectively. The spleen weight to body weight ratios and anti-double-stranded DNA autoantibody titres were found to be significantly higher in the autoimmune models than in the control strains. Furthermore, the autoimmune model presented prominent MFALCs, with a significantly greater ratio of lymphoid cluster area to total mediastinal fat tissue area, and more apparent diffused cellular infiltration into the lung lobes than the other studied strains. Higher numbers of T and B cells, macrophages and proliferating cells, but fewer granulocytes, were observed in the autoimmune models than in the control strains. Interestingly, a significant positive Pearson's correlation between the size of the MFALCs and the density of CD3-, B220- and Iba1-positive cells in the lung was observed. Therefore, our data suggest a potentially important role for MFALCs in the progression of lung disease. However, further investigation is required to clarify the pathological role of MFALCs in lung disease, especially in inflammatory disorders.
  • Ken-ichi Otsuguro, Yuki Tomonari, Saori Otsuka, Soichiro Yamaguchi, Yasuhiro Kon, Shigeo Ito
    NEUROPHARMACOLOGY 97 160 - 170 0028-3908 2015/10 [Refereed][Not invited]
     
    Adenosine kinase (AK) inhibitor is a potential candidate for controlling pain, but some AK inhibitors have problems of adverse effects such as motor impairment. ABT-702, a non-nucleoside AK inhibitor, shows analgesic effect in animal models of pain. Here, we investigated the effects of ABT-702 on synaptic transmission via nociceptive and motor reflex pathways in the isolated spinal cord of neonatal rats. The release of adenosine from the spinal cord was measured by HPLC. ABT-702 inhibited slow ventral root potentials (sVRPs) in the nociceptive pathway more potently than monosynaptic reflex potentials (MSRs) in the motor reflex pathway. The inhibitory effects of ABT-702 were mimicked by exogenously applied adenosine, blocked by 8CPT (8-cyclopentyl-1,3-dipropylxanthine), an adenosine A(1) receptor antagonist, and augmented by EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine), an adenosine deaminase (ADA) inhibitor. Equilibrative nucleoside transporter (ENT) inhibitors reversed the effects of ABT-702, but not those of adenosine. ABT-702 released adenosine from the spinal cord, an effect that was also reversed by ENT inhibitors. The ABT-702-facilitated release of adenosine by way of ENTs inhibits nociceptive pathways more potently than motor reflex pathways in the spinal cord via activation of A1 receptors. This feature is expected to lead to good analgesic effects, but, caution may be required for the use of AK inhibitors in the case of ADA dysfunction or a combination with ENT inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.
  • M. Chihara, T. Nakamura, S. Otsuka-Kanazawa, O. Ichii, Y. H. A. Elewa, Y. Kon
    ANDROLOGY 3 (5) 991 - 999 2047-2919 2015/09 [Refereed][Not invited]
     
    MRL/MpJ mice possess highly heat-shock-resistant spermatocytes (HRS) in comparison with C57BL/6 mice. This resistance depends on the MRL/MpJ-type loci at the 81 cM region of Chromosome (Chr) 1 and the 40 cM region of Chr 11. To evaluate the functions of these loci in detail, we examined the histopathological changes resulting from experimental cryptorchidism or transient scrotal heat stress (SHS) in the testes of C57BL/6-based congenic strains (B6.MRLc1, B6.MRLc11, and B6.MRLc1c11) carrying the MRL/MpJ-derived loci responsible for HRS. Among cryptorchid testes from congenic strains, those in B6.MRLc1c11 mice showed the highest heat resistance, indicating that the genetic interactions between MRL/MpJ-derived HRS loci on Chrs 1 and 11 may be important for maintaining spermatogenesis under continuous testicular hyperthermia. In contrast, immediately after SHS induction, germ cell loss via apoptosis was inhibited in B6.MRLc11 and B6.MRLc1c11 mice, similar to that in MRL/MpJ mice. However, this HRS phenotype was not observed in C57BL/6 or B6.MRLc1 mice after SHS induction. Furthermore, testicular calcification owing to long-term damage by SHS induction was inhibited in all congenic strains in comparison with that in C57BL/6 mice, indicating that each MRL/MpJ-derived locus on Chrs 1 and 11 acted independently to facilitate the recovery of heat-induced testicular damage by inhibiting calcification. B6.MRLc11 and B6.MRLc1c11 mice showed greater recovery in spermatogenesis than B6.MRLc1 mice 60 days after SHS induction. Therefore, the MRL/MpJ-derived HRS locus on Chr 11 might play an important role in recovery from heat stress damage. On the basis of these results, we concluded that MRL/MpJ-derived loci on Chrs 1 and 11 cooperatively or independently regulate testicular heat sensitivity depending on the various heat stresses.
  • Saori Otsuka-Kanazawa, Osamu Ichii, Yasuhiro Kon
    MECHANISMS OF DEVELOPMENT 137 23 - 32 0925-4773 2015/08 [Refereed][Not invited]
     
    In general, mammalian males produce only spermatozoa in their testes and females produce only oocytes in their ovaries. However, newborn MRL/MpJ male mice produce oocytes within their testes. In this study, we examined the initiation and progression of oogenesis in fetal and neonatal MRL/MpJ mouse testes and evaluated the characteristics of testicular oocytes. Germ cells with positive reactions to oogenesis markers such as NOBOX oogenesis homeobox and synaptonemal complex protein 3 were observed in the MRL/MpJ fetal testes on embryonic day 18.5. These fetal testicular oocytes possessed maternal-specific methylation patterns of histone and DNA. The level of DNA methylation was still low in postnatal testicular oocytes at day 14 after birth. Additionally, the postnatal testicular oocytes contained both X and Y chromosomes and had the ability to fuse with sperm. These results suggest that some XY germ cells in fetal testes of MRL/MpJ mice enter meiosis prematurely, undergo oogenesis, and differentiate into oocytes. In addition, MRL/MpJ testicular oocytes have the ability to carry on oogenesis before and shortly after birth until they obtain some of the morphological, epigenetic, and functional characteristics of oocytes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Sawa Onouchi, Osamu Ichii, Saori Otsuka-Kanazawa, Yasuhiro Kon
    CELL AND TISSUE RESEARCH 360 (2) 273 - 285 0302-766X 2015/05 [Refereed][Not invited]
     
    The asymmetric shape of component cells determines the asymmetric features of developing organs. Here, we focused on the murine duodenojejunal flexure (DJF), which bends without affecting the mesentery, and analyzed the morphological asymmetries of the mucosal epithelium and gut wall cells between the inner and outer bending sides at embryonic days 10.75-11.75. In the mucosal epithelium, the cell shape and the expression of epithelial markers (Cdx2, Ecadherin) showed no differences between the two DJF sides. In contrast, the gut wall cells comprising the inner and outer sides of the DJF were elongated along the inner-outer axis and perpendicular to this axis, respectively. Furthermore, the gut wall cells in the outer side possessed cytoplasmic processes connecting cells via adherens junctions, but those in the inner side were attached via adherens junctions of juxtaposed cell bodies and were relatively more crowded. In immunohistochemistry experiments, there was no remarkable difference in the positive reactions of markers for mesenchyme (vimentin), smooth muscle cells (alpha SMA), endothelial cells (LYVE-1, CD34), and undifferentiated neurons (Sox10) between the DJF sides. Interestingly, Tuj1-positive cells, indicating differentiated neurons, were observed in the middle layer of the gut wall, and these cells were significantly more abundant and tended to be larger in the inner side than in the outer side of the DJF. In conclusion, we clarified the asymmetries of gut wall cell morphology and neural differentiation between the inner and outer sides of the DJF. These characteristics of the developing murine DJF indicate its asymmetric formation.
  • Otani Y, Ichii O, Otsuka-Kanazawa S, Chihara M, Nakamura T, Kon Y
    Autoimmunity 1 - 10 0891-6934 2015/04 [Refereed][Not invited]
  • Yuma Yamashita, Teppei Nakamura, Saori Otsuka-Kanazawa, Osamu Ichii, Yasuhiro Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 63 (1) 25 - 36 0047-1917 2015/02 [Refereed][Not invited]
     
    In perinatal mice, the ovary undergoes drastic morphological changes, as clusters of oocytes called nests break into smaller cysts and subsequently form individual follicles. We studied perinatal oocyte development in MRL/MpJ mice, and compared it to that observed in C57BL/6 mice between embryonic day 18.5 and postnatal day 4. Throughout the observation period, compared to C57BL/6 mice, MRL/MpJ mice displayed significantly fewer oocytes in their ovaries. Morphologically, there were no clear differences between the strains at embryonic day 18.5. However, the beginning of folliculogenesis, as evidenced by the expression of NOBOX. oogenesis homeobox (Nobox) transcript and protein, was more enhanced in MRL/MpJ mice than in C57BL/6 mice at embryonic day 18.5 and postnatal day 0. In addition, developed follicles were more frequently observed in MRL/MpJ mice than in C57BL/6 mice between postnatal days 0 and 4. In conclusion, the oocyte development during nest breakdown and folliculogenesis was accelerated in MRL/MpJ mice when compared to that observed in C57BL/6 mice.
  • Junpei Kimura, Osamu Ichii, Kosuke Miyazono, Teppei Nakamura, Taro Horino, Saori Otsuka-Kanazawa, Yasuhiro Kon
    SCIENTIFIC REPORTS 4 7290  2045-2322 2014/12 [Refereed][Not invited]
     
    Members of the Toll-like receptor (TLR) family serve as pathogen sensors and participate in local autoimmune responses. This study found a correlation between glomerular injury and TLR expression by analysing BXSB/MpJ-Yaa (BXSB-Yaa) lupus model mice. In isolated glomeruli, the mRNA expression of several TLRs was higher in BXSB-Yaa mice than in healthy control BXSB mice. In particular, the expression of Tlr8 and its downstream cytokines was markedly increased. In mouse kidneys, TLR8 protein and mRNA localized to podocytes, and TLR8 protein expression in the glomerulus was higher in BXSB-Yaa mice than in BXSB mice. In BXSB-Yaa mice, the glomerular levels of Tlr8 mRNA negatively correlated with the glomerular levels of podocyte functional markers (Nphs1, Nphs2, and Synpo) and positively correlated with urinary albumin levels. Furthermore, the glomerular and serum levels of miR-21, a putative microRNA ligand of TLR8, were higher in BXSB-Yaa mice than in BXSB mice. The urinary levels of Tlr8 mRNA were also higher in BXSB-Yaa mice than in BXSB mice. In conclusion, the overexpression of TLR8 correlates with the progression of podocyte injury in glomerulonephritis. Thus, altered levels of urinary Tlr8 mRNA might reflect podocyte injury.
  • Osamu Ichii, Saori Otsuka-Kanazawa, Taro Horino, Junpei Kimura, Teppei Nakamura, Manabu Matsumoto, Makoto Toi, Yasuhiro Kon
    PLOS ONE 9 (10) e110383  1932-6203 2014/10 [Refereed][Not invited]
     
    MicroRNAs contribute to the pathogenesis of certain diseases and may serve as biomarkers. We analyzed glomerular microRNA expression in B6. MRLc1, which serve as a mouse model of autoimmune glomerulonephritis. We found that miR-26a was the most abundantly expressed microRNA in the glomerulus of normal C57BL/6 and that its glomerular expression in B6. MRLc1 was significantly lower than that in C57BL/6. In mouse kidneys, podocytes mainly expressed miR-26a, and glomerular miR-26a expression in B6. MRLc1 mice correlated negatively with the urinary albumin levels and podocyte-specific gene expression. Puromycin-induced injury of immortalized mouse podocytes decreased miR-26a expression, perturbed the actin cytoskeleton, and increased the release of exosomes containing miR-26a. Although miR-26a expression increased with differentiation of immortalized mouse podocytes, silencing miR-26a decreased the expression of genes associated with the podocyte differentiation and formation of the cytoskeleton. In particular, the levels of vimentin and actin significantly decreased. In patients with lupus nephritis and IgA nephropathy, glomerular miR-26a levels were significantly lower than those of healthy controls. In B6. MRLc1 and patients with lupus nephritis, miR-26a levels in urinary exosomes were significantly higher compared with those for the respective healthy control. These data indicate that miR-26a regulates podocyte differentiation and cytoskeletal integrity, and its altered levels in glomerulus and urine may serve as a marker of injured podocytes in autoimmune glomerulonephritis.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    CELL AND TISSUE RESEARCH 357 (3) 731 - 741 0302-766X 2014/09 [Refereed][Not invited]
     
    The association between adipose tissue and immunity has been established and fat-associated lymphoid clusters (FALCs) are considered as a source of immune cells. We discovered lymphoid clusters (LCs) in mouse mediastinal fat tissues (MFTs). In Th1-biased C57BL/6N (B6), Th2-biased DBA/2Cr (DBA) and autoimmune-prone MRL/MpJ (MRL) mice strains, LCs without a fibrous capsule and germinal center were observed in white-colored MFTs extending from the diaphragm to the heart. The number and size of the LCs were larger in 12-month-old mice than in 3-month-old mice in all of the examined strains. Moreover, B6 had an especially large number of LCs compared with DBA and MRL. The immune cells in the LCs consisted of mainly T-cells and some B-cells. The majority of T-cells were CD4+ helper T (Th) cells, rather than CD8+ cytotoxic T-cells and no obvious immune cell population difference was present among the strains. Furthermore, high endothelial venules and lymphatic vessels in the LCs were better developed in B6 mice than in the other strains. Interestingly, some CD133+ hematopoietic progenitor cells and some c-Kit+/CD127+ natural helper cells were detected in the LCs. BrdU+ proliferating cells were more abundant in the LCs of B6 mice than in the LCs of the other strains and the number of BrdU+ cells increased with age. This is the first report of LCs in mouse MFTs. We suggest that the mouse genetic background affects LC size and number. We term the LCs "mediastinal fat-associated lymphoid clusters". These clusters can be considered as niches for Th cell production.
  • Masataka Chihara, Teppei Nakamura, Naoki Sakakibara, Saori Otsuka, Osamu Ichii, Yasuhiro Kon
    AMERICAN JOURNAL OF PATHOLOGY 184 (9) 2480 - 2492 0002-9440 2014/09 [Refereed][Not invited]
     
    Spermatocytes of MRL/MpJ mice are more heat resistant than those of C57BL/6 mice in experimental cryptorchidism. This phenotype depends in part on the locus at the 81-cM region of MRL/MpJ-type chromosome 1 (Chr 1). To evaluate the function of this locus, we examined pathological changes in mouse testes resulting from transient scrotal heat stress. Immediately after scrotal heat stress, meiosis progression and blood-testis barrier integrity were preserved in MRL/MpJ but not in C57BL/6 mice, nor in a C57BL/6-based congenic strain carrying the MRL/MpJ-derived Chr 1 locus (B6.MRLc1). Testicular damage was severe in the weeks after scrotal heat stress in all three strains; however, testicular calcification was observed only in C57BL/6 and MRL/MpJ mice (initially as nanocrystals in mitochondria of degenerating germ cells). In testes, expression of gremlin 2, a bone morphogenetic protein antagonist encoded on Chr 1, was markedly higher in B6.MRLc1 than in C57BL/6 or MRL/Mp3 mice. Furthermore, gremlin-2 and bone morphogenetic protein 2 mRNA levels in heated testes correlated negatively and positively, respectively, with calcification. Thus, although the MRL/MpJ-derived Locus on Chr 1 may play a pivotal role in recovery from heat-induced testicular damage, especially via inhibition of calcification, MRL/MpJ mice have a precipitating factor for testicular calcification and heat shock-resistant factors that reside outside the 81-cM region of Chr 1.
  • Osamu Ichii, Saori Otsuka-Kanazawa, Teppei Nakamura, Masaaki Ueno, Yasuhiro Kon, Weiping Chen, Avi Z. Rosenberg, Jeffrey B. Kopp
    PLOS ONE 9 (9) e108448  1932-6203 2014/09 [Refereed][Not invited]
     
    Indoxyl sulfate is a uremic toxin and a ligand of the aryl-hydrocarbon receptor (AhR), a transcriptional regulator. Elevated serum indoxyl sulfate levels may contribute to progressive kidney disease and associated vascular disease. We asked whether indoxyl sulfate injures podocytes in vivo and in vitro. Mice exposed to indoxyl sulfate for 8 w exhibited prominent tubulointerstitial lesions with vascular damage. Indoxyl sulfate-exposed mice with microalbuminuria showed ischemic changes, while more severely affected mice showed increased mesangial matrix, segmental solidification, and mesangiolysis. In normal mouse kidneys, AhR was predominantly localized to the podocyte nuclei. In mice exposed to indoxyl sulfate for 2 h, isolated glomeruli manifested increased Cyp1a1 expression, indicating AhR activation. After 8 w of indoxyl sulfate, podocytes showed foot process effacement, cytoplasmic vacuoles, and a focal granular and wrinkled pattern of podocin and synaptopodin expression. Furthermore, vimentin and AhR expression in the glomerulus was increased in the indoxyl sulfate-exposed glomeruli compared to controls. Glomerular expression of characteristic podocyte mRNAs was decreased, including Actn4, Cd2ap, Myh9, Nphs1, Nphs2, Podxl, Synpo, and Wt1. In vitro, immortalized-mouse podocytes exhibited AhR nuclear translocation beginning 30 min after 1 mM indoxyl sulfate exposure, and there was increased phospho-Rac1/Cdc42 at 2 h. After exposure to indoxyl sulfate for 24 h, mouse podocytes exhibited a pro-inflammatory phenotype, perturbed actin cytoskeleton, decreased expression of podocyte-specific genes, and decreased cell viability. In immortalized human podocytes, indoxyl sulfate treatment caused cell injury, decreased mRNA expression of podocyte-specific proteins, as well as integrins, collagens, cytoskeletal proteins, and bone morphogenetic proteins, and increased cytokine and chemokine expression. We propose that basal levels of AhR activity regulate podocyte function under normal conditions, and that increased activation of podocyte AhR by indoxyl sulfate contributes to progressive glomerular injury.
  • Y. H. A. Elewa, O. Ichii, S. Otsuka, Y. Hashimoto, Y. Kon
    ANATOMIA HISTOLOGIA EMBRYOLOGIA 43 (4) 265 - 272 0340-2096 2014/08 [Refereed][Not invited]
     
    Previously, the structure of the adult goat parotid salivary glands (PGs) was studied. However, little information was elucidated of the juvenile ones. This study aimed to clarify the correlations between the structure of goats' PGs and the nature of food intake among milk-suckling kids (MSKs) and diet-fed goats (DFGs). The secretory endpieces of the goats' PGs are of the pure serous type. The serous cells in MSKs showed apical accumulation of numerous secretory granules (SGs) of smaller size and of more intense positive periodic acid-Schiff reaction. Ultrastructurally, most of the SGs in the DFGs contained peripherally located inclusions that showed dense reaction products for acid phosphatase. In MSKs, the PGs showed less-developed basal infoldings, sparseness of the inter-cellular inter-digitations, fewer inter-cellular canaliculi and microvilli and also less-developed myoepithelial cells with fewer and shorter cytoplasmic processes. In conclusion, the less-developed membrane specializations and myoepithelial cells, as well as the accumulated SGs in the PGs of MSKs, suggest that it secretes less saliva with a little secretory activity than that of DFGs, which may be correlated with the reduced masticatory activity.
  • Teppei Nakamura, Yuko Sakata, Saori Otsuka-Kanazawa, Osamu Ichii, Masataka Chihara, Ken-ichi Nagasaki, Yuka Namiki, Yasuhiro Kon
    PLOS ONE 9 (6) e100617  1932-6203 2014/06 [Refereed][Not invited]
     
    In MRL/MpJ mice, ovarian mast cells (OMCs) are more abundant than in other mouse strains, and tend to distribute beneath the ovarian surface epithelium at birth. This study investigated the factors regulating the appearance of neonatal OMCs in progeny of the cross between MRL/MpJ and C57BL/6N strains. F1 neonates had less than half the number of OMCs than MRL/MpJ. Interestingly, MRLB6F1 had more neonatal OMCs than B6MRLF1, although they were distributed over comparable areas. Furthermore, in MRL/MpJ fetuses for which parturition was delayed until embryonic day 21.5, the number of OMCs was significantly higher than in age-matched controls at postnatal day 2. These results suggest that the number of OMCs was influenced by the environmental factors during pregnancy. Quantitative trait locus analysis using N2 backcross progeny revealed two significant loci on chromosome 8: D8Mit343-D8Mit312 for the number of OMCs and D8Mit86-D8Mit89 for their distribution, designated as mast cell in the ovary of MRL/MpJ 1 (mcom1) and mcom2, respectively. Among MC migration-associated genes, ovarian expression of chemokine (C-C motif) ligand 17 at mcom1 locus was significantly higher in MRL/MpJ than in C57BL/6N, and positively correlated with the expression of OMC marker genes. These results indicate that the appearance of neonatal OMCs in MRL/MpJ is controlled by environmental factors and filial genetic factors, and that the abundance and distribution of OMCs are regulated by independent filial genetic elements.
  • Keigo Kosenda, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 41 (8) 788 - 797 1442-6404 2013/11 [Refereed][Not invited]
     
    BackgroundDacryoadenitis is characteristic of an autoimmune exocrinopathy, e.g. Sjogren syndrome. We pathologically examined the lacrimal glands of autoimmune-prone BXSB/MpJ-Yaa mice for the appearance of pathological signs of dacryoadenitis progression in autoimmune dacryoadenitis models, particularly focusing on messenger RNAs in the lacrimal fluid. MethodsThe lacrimal glands of the BXSB/MpJ-Yaa and C57BL/6 mice were histopathologically analyzed in parallel with the evaluation of lacrimation and messenger RNA expression of water channels (Aqp3, Aqp4 and Aqp5). In addition, autoimmune model mice (MRL/MpJ-lpr/lpr and NZB/NZWF1) were used for evaluating cell infiltration and detecting inflammatory cell marker messenger RNAs (Cd68, Ptprc and Cd3e) in the lacrimal fluids by polymerase chain reaction-based methods. ResultsB-cell predominant lymphocytic infiltrations and the destruction of acini were observed in the lacrimal glands of BXSB/MpJ-Yaa mice. There was no significant difference in the quantity of lacrimal fluid between the BXSB/MpJ-Yaa and C57BL/6 mice. In the BXSB/MpJ-Yaa mice, Aqp3 expression increased significantly with the cell infiltration score, whereas expression of Aqp4 and Aqp5 tended to decrease. Aqp3 expression increased significantly with the cell infiltration score in BXSB/MpJ-Yaa mice. Among inflammatory cell markers, Cd68 was more frequently detected in the lacrimal fluid of the BXSB/MpJ-Yaa, MRL/MpJ-lpr/lpr and NZB/NZWF1 mice than in that of the C57BL/6 mice. ConclusionBXSB/MpJ-Yaa mice clearly developed autoimmune dacryoadenitis. The altered expression of water channels in lacrimal glands might be associated with the preservation of lacrimal fluid excretion in BXSB/MpJ-Yaa mice. The detection of inflammatory cell markers in lacrimal fluid could be used as a diagnostic marker for autoimmune dacryoadenitis.
  • Yuki Naganuma, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    JOURNAL OF VETERINARY MEDICAL SCIENCE 75 (3) 283 - 290 0916-7250 2013/03 [Refereed][Not invited]
     
    Caspase activation is associated with skeletal muscle differentiation in mouse embryos. We examined the relationship between cardiac myogenesis and cell death using mice hearts at embryonic days (E) 11.5-15.5 and fetal rat heart H9C2 cells. The number of TdT-mediated dUTP nick erid labeling (TUNEL)-positive cells increased with fetal age and was much higher than that of single-stranded DNA (ssDNA)- and active caspase-3 (aCasp3)-positive cells. TUNEL and aCasp3 double staining resulted in 3 types of positive cells: TUNEL+/aCasp3(+), TUNEL+/aCasp3(-) and TUNEL-/aCasp3(+). TUNEL+/aCasp3(-) cells were the most common but lacked morphological features of apoptosis, such as nuclear condensation or fragmentation. The expression of anti-apoptotic factors increased during E11.5-15.5. Furthermore, TUNEL-positive H9C2 cells without nuclear condensation or fragmentation were observed only in myotubes later in the culture period. In this study, the dynamics of TUNEL-positive cardiomyocyte was inconsistent with the activation of apoptosis cascade, and their morphological feature was clearly different from representative apoptosis. From these findings, we concluded that the increased number of TUNEL-positive cardiomyocyte, having the DNA strand breaks, would be associated with the progression of cardiac myogenesis.
  • Kimura, J, Ichii, O, Otsuka, S, Sasaki, H, Hashimoto, Y, Kon, Y
    Am. J. Nephrol. 38 (1) 27 - 38 2013 [Refereed][Not invited]
  • Mice stage-specific claudin 3 expression regulates progression of meiosis in early stage spermatocytes.
    Chihara, M, Ikebuchi, R, Otsuka, S, Ichii, O, Hashimoto, Y, Suzuki, A, Saga, Y, Kon, Y
    Biol. Reprod. 89 (1) 1 - 12 2013 [Refereed][Not invited]
  • Saori Otsuka, Osamu Ichii, Yuka Namiki, Nobuya Sasaki, Yoshiharu Hashimoto, Yasuhiro Kon
    MAMMALIAN GENOME 23 (11-12) 741 - 748 0938-8990 2012/12 [Refereed][Not invited]
     
    Mammals produce sperm or oocytes depending on their sex; however, newborn MRL/MpJ (MRL) male mice produce oocytes within their testes. We previously reported that one of the genes responsible for this phenotype is present on the MRL-type Y chromosome (Y-MRL), and that multiple genes, probably autosomal, are also required for the development of this phenotype. In this study we focused on the autosomal genes and examined their relationship with this phenotype by analyzing the progeny from crosses between MRL mice and other strains. We first observed the male F1 progeny from the crosses between female A/J, C57BL/6 (B6), BALB/c, C3H/He, or DBA/2 mice and male MRL mice, and two consomic strains, male B6-Y-MRL and MRL-Y-B6. Testicular oocytes that were morphologically similar to those of MRL mice were detected in all mouse strains except BALBMRLF1; however, the incidence of testicular oocytes was significantly lower than that in MRL mice. The appearance of testicular oocytes in MRL-Y-B6 mice indicates that this phenotype is strongly affected by genomic factors present on autosomes, and that there is at least one other causative gene on the MRL-type autosomes (MRL testicular oocyte production, mtop) other than that on Y-MRL. Furthermore, a quantitative trait locus (QTL) analysis using N2 backcross progeny from crosses between female MRLB6F1 and male MRL mice revealed the presence of susceptibility loci for the appearance of testicular oocytes at 8-17 cM on Chr 15. These findings demonstrate that the appearance of testicular oocytes is regulated by the genetic factors on Chr 15 and on Y-MRL.
  • Osamu Ichii, Saori Otsuka, Nobuya Sasaki, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    KIDNEY INTERNATIONAL 81 (3) 280 - 292 0085-2538 2012/02 [Refereed][Not invited]
     
    MicroRNAs (miRNAs) are highly conserved small non-coding RNAs that act as post-transcriptional regulators of target mRNA. In this study, we sought to identify the microRNA underlying local inflammation in a murine model of chronic kidney disease (CKD). In microarray analysis of kidneys, the expression of miR-146a/b was elevated in B6.MRLc1 CKD mice that spontaneously develop renal inflammation with age. Primary-microRNA analysis found that elevated miR-146a/b expression in the kidneys of B6.MRLc1 mice was mainly derived from miR-146a rather than miR-146b, and this expression increased with the development of CKD. Histopathological scores for glomerular and interstitial lesions, mRNA expression of inflammatory mediators, and macrophage infiltration were significantly higher in B6.MRLc1 than C57BL/6 mice and were positively correlated with miR-146a expression. In situ hybridization and laser microdissection-RT-PCR showed that miR-146a expression in interstitial lesions containing inflammatory cells was higher than in the glomerulus. The increased expression of the inflammatory-associated genes RELA, IRAK1, IL1B, IL10, and CXCLs was noted in miR-146a/b-silenced human monocytes. The amount of miR-146a was higher in urine sediments of B6.MRLc1 than of C57BL/6 mice. Thus, miR-146a expression in the kidneys and its urinary excretion was specifically associated with the development of interstitial lesions and correlated with inflammatory cell infiltration. Kidney International (2012) 81, 280-292; doi: 10.1038/ki.2011.345; published online 5 October 2011
  • Tomohiro Nishino, Nobuya Sasaki, Ken-ichi Nagasaki, Osamu Ichii, Yasuhiro Kon, Takashi Agui
    BIOMEDICAL RESEARCH-TOKYO 33 (1) 53 - 56 0388-6107 2012/02 [Refereed][Not invited]
     
    The ICGN mouse strain is a glomerulosclerosis (GS) model that shows significant proteinuria, podocyte morphological abnormalities and increased extracellular matrix accumulation in the glomeruli, which represent the final common pathology associated with a variety of kidney diseases leading to end-stage renal failure. Previously, we demonstrated that GS in ICGN mice can be attributed to the deletion mutation of the tensin2 (Tns2) gene (Tns2(nep)). Further, the C57BL/6J (B6) mouse is resistant to GS caused by this mutation. 129/Sv is also a popular strain; however, its susceptibility to GS has not been defined. Thus, to determine whether 129/Sv is resistant or susceptible to GS, we produced a congenic strain carrying Tns2(nep)) on the 129(+Ter)/Sv (129T) background. 129T congenic mice (129T-Tns2(nep)) did not exhibit albuminuria, renal anemia, increases in BUN, or any severe pathological changes until at least 16 weeks of age. These results indicate that 1291 is resistant to GS. Although their usage in biomedical studies is already widespread, 129/Sv mice may afford a late-onset and unique strain applicable to kidney disease research.
  • Nishino T, Sasaki N, Chihara M, Nagasaki K, Torigoe D, Kon Y, Agui T
    Experimental animals / Japanese Association for Laboratory Animal Science 5 61 (5) 525 - 532 1341-1357 2012 [Refereed][Not invited]
  • Shin-Hyo Lee, Osamu Ichii, Saori Otsuka, Elewa Yaser Hosney, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    JOURNAL OF ANATOMY 219 (6) 743 - 755 0021-8782 2011/12 [Not refereed][Not invited]
     
    MRL/MpJ (MRL) mice, commonly used as a model for autoimmune disease, have a high frequency of ovarian cysts originating from the rete ovarii. In the present study, to clarify how the rete ovarii, which are remnants of mesonephric tubules during embryogenesis, progress to cystic formation with aging, the morphology of MRL rete ovarii was analyzed and compared with that of normal C57BL/6N (B6) mice. In B6 mice, the rete ovarii consisted of a series of tubules, including the extraovarian rete (ER), the connecting rete (CR), and the intraovarian rete (IR), based on their location. Whereas the ER of B6 mice was composed of highly convoluted tubules lined by both ciliated and non-ciliated epithelia, the tubules in the CR and IR had only non-ciliated cells. In MRL mice, dilations of the rete ovarii initiated from the IR rather than the ER or CR. Although the histological types of cells lining the lumen of the rete ovarii were the same as those in B6 mice, the ER in MRL mice showed a variety in morphology. In particular, the connections between the ER and ovary tended to disappear with increasing age and the development of ovarian cysts. Furthermore, the epithelium lining the large ovarian cysts in MRL mice had ciliated cells forming the cluster. On the basis of these findings, it is suggested that cystic changes of the rete ovarii in MRL mice are caused by the dilations of the IR with invasion of the ER and CR into the ovarian medulla. These data provide new pathological mechanisms for ovarian cyst formation.
  • Shin-Hyo Lee, Osamu Ichii, Saori Otsuka, Elewa Yaser Hosney, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    JOURNAL OF ANATOMY 6 219 (6) 743 - 755 0021-8782 2011/12 [Refereed][Not invited]
     
    MRL/MpJ (MRL) mice, commonly used as a model for autoimmune disease, have a high frequency of ovarian cysts originating from the rete ovarii. In the present study, to clarify how the rete ovarii, which are remnants of mesonephric tubules during embryogenesis, progress to cystic formation with aging, the morphology of MRL rete ovarii was analyzed and compared with that of normal C57BL/6N (B6) mice. In B6 mice, the rete ovarii consisted of a series of tubules, including the extraovarian rete (ER), the connecting rete (CR), and the intraovarian rete (IR), based on their location. Whereas the ER of B6 mice was composed of highly convoluted tubules lined by both ciliated and non-ciliated epithelia, the tubules in the CR and IR had only non-ciliated cells. In MRL mice, dilations of the rete ovarii initiated from the IR rather than the ER or CR. Although the histological types of cells lining the lumen of the rete ovarii were the same as those in B6 mice, the ER in MRL mice showed a variety in morphology. In particular, the connections between the ER and ovary tended to disappear with increasing age and the development of ovarian cysts. Furthermore, the epithelium lining the large ovarian cysts in MRL mice had ciliated cells forming the cluster. On the basis of these findings, it is suggested that cystic changes of the rete ovarii in MRL mice are caused by the dilations of the IR with invasion of the ER and CR into the ovarian medulla. These data provide new pathological mechanisms for ovarian cyst formation.
  • Osamu Ichii, Saori Otsuka, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    PLOS ONE 6 (11) e27783  1932-6203 2011/11 [Not refereed][Not invited]
     
    Primary causes of urinary tract obstruction that induces urine retention and results in hydronephrosis include uroliths, inflammation, and tumors. In this study, we analyzed the molecular pathology of ureteritis causing hydronephrosis in laboratory rodents. F2 progenies of C57BL/6 and DBA/2 mice were studied histopathologically and by comprehensive gene expression analysis of their ureters. Incidence of hydronephrosis was approximately 5% in F2 progenies. Histopathologically, this hydronephrosis was caused by stenosis of the proximal ureter, which showed fibrosis and papillary malformations of the proliferative epithelium with infiltrations of B-cell-dominated lymphocytes. Additionally, CD16-positive large granular leukocytes and eosinophils infiltrated from the ureteral mucosa to the muscular layer. Eosinophilic crystals were characteristically observed in the lumen of the ureter and the cytoplasm of large granular leukocytes, eosinophils, and transitional epithelial cells. Comprehensive gene profiling revealed remarkably elevated expression of genes associated with hyperimmune responses through activation of B cells in diseased ureters. Furthermore, diseased ureters showed dramatically higher gene expression of chitinase 3-like 3, known as Ym1, which is associated with formation both of adenomas in the transitional epithelium and of eosinophilic crystals in inflammatory conditions. The Ym1 protein was mainly localized to the cytoplasm of the transitional epithelium, infiltrated cells, and eosinophilic crystals in diseased ureters. We determined that the primary cause of hydronephrosis in F2 mice was ureteritis mediated by the local hyperimmune response with malformation of the transitional epithelium. Our data provide a novel molecular pathogenesis for elucidating causes of aseptic inflammation in human upper urinary tracts.
  • Osamu Ichii, Saori Otsuka, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    PLOS ONE 6 (11) e27783  1932-6203 2011/11 [Refereed][Not invited]
     
    Primary causes of urinary tract obstruction that induces urine retention and results in hydronephrosis include uroliths, inflammation, and tumors. In this study, we analyzed the molecular pathology of ureteritis causing hydronephrosis in laboratory rodents. F2 progenies of C57BL/6 and DBA/2 mice were studied histopathologically and by comprehensive gene expression analysis of their ureters. Incidence of hydronephrosis was approximately 5% in F2 progenies. Histopathologically, this hydronephrosis was caused by stenosis of the proximal ureter, which showed fibrosis and papillary malformations of the proliferative epithelium with infiltrations of B-cell-dominated lymphocytes. Additionally, CD16-positive large granular leukocytes and eosinophils infiltrated from the ureteral mucosa to the muscular layer. Eosinophilic crystals were characteristically observed in the lumen of the ureter and the cytoplasm of large granular leukocytes, eosinophils, and transitional epithelial cells. Comprehensive gene profiling revealed remarkably elevated expression of genes associated with hyperimmune responses through activation of B cells in diseased ureters. Furthermore, diseased ureters showed dramatically higher gene expression of chitinase 3-like 3, known as Ym1, which is associated with formation both of adenomas in the transitional epithelium and of eosinophilic crystals in inflammatory conditions. The Ym1 protein was mainly localized to the cytoplasm of the transitional epithelium, infiltrated cells, and eosinophilic crystals in diseased ureters. We determined that the primary cause of hydronephrosis in F2 mice was ureteritis mediated by the local hyperimmune response with malformation of the transitional epithelium. Our data provide a novel molecular pathogenesis for elucidating causes of aseptic inflammation in human upper urinary tracts.
  • Pathological correlations between podocyte injuries and renal functions in canine and feline chronic kidney diseases
    Osamu Ichii, Akira Yabuki, Nobuya Sasaki, Saori Otsuka, Hiroshi Ohta, Masahiro Yamasaki, Mitsuyoshi Takiguchi, Yuka Namiki, Yoshiharu Hashimoto, Daiji Endoh, Yasuhiro Kon
    HISTOLOGY AND HISTOPATHOLOGY 26 (10) 1243 - 1255 0213-3911 2011/10 [Not refereed][Not invited]
     
    Podocytes cover the glomerulus and their adjacent foot processes form a principal barrier called the slit diaphragm. Podocyte dysfunctions, including podocyte loss and slit diaphragm disruptions, induce chronic kidney diseases (CKD). In this study, we analyzed the correlations between podocyte injuries and renal dysfunctions in domestic carnivores. Dogs and cats were divided into normal and CKD groups according to renal histopathology and plasma creatinine values. Immunostaining results showed that linear reactions of slit diaphragm molecules, e. g., nephrin, podocin, and ACTN4, were parallel to glomerular capillaries in all animals. However, in dogs, reactions of nephrin and ACTN4 were changed to a granular pattern in the CKD group, and their intensities significantly decreased with the number of podocytes in the glomerulus. Moreover, the expression of nephrin and ACTN4 negatively correlated with creatinine. Real-time PCR analysis showed that nephrin mRNA expression in the kidneys of CKD dogs was significantly lower than that in normal animals, and negatively correlated with creatinine. Although no significant correlation between renal dysfunction and podocyte injury was detected in cats, histoplanimetric scores of tubulointerstitial lesions in CKD cats were higher than those in both normal cats and diseased dogs. Furthermore, mRNAs of WT1 and SD molecules were detected in urine from CKD animals. In conclusion, podocyte injuries such as podocytopenia and decreased expression of nephrin and ACTN4 in the glomerulus were more strongly correlated with renal dysfunction in dogs than in cats. These findings suggest that the CKD pathogenesis, especially susceptibilities to podocyte injuries, differed between dogs and cats.
  • Ayo Yila Simon, Nobuya Sasaki, Osamu Ichii, Kiichi Kajino, Yasuhiro Kon, Takashi Agui
    MICROBES AND INFECTION 13 (8-9) 783 - 797 1286-4579 2011/08 [Refereed][Not invited]
     
    Respiratory viral infections result in severe pulmonary injury, to which host immune response may be a significant contributor. At present, it is not entirely clear the extent to which lung injury is a necessary consequence of host defense. In this report, we use functional genomics approach to characterize the key roles of cellular immunity and immune-inflammatory response in the immunopathology of Sendai virus infection in resistant C57BL/6J and susceptible DBA/2J mice. Infected mice manifested an immune-inflammatory response characterized by the pulmonary influx of neutrophils and mononuclear cells. DBA/2J mice mounted a vigorous immune response, with significant up-regulation of cytokine/chemokine genes in two successive waves through the course of infection. Whereas, C57BL/6J mice displayed an efficient immune response with less severe pathology and clusters of immune-inflammatory responsive genes were exclusively up-regulated on day 4 in this strain. Overall, DBA/2J mice exhibited a dysregulated hyper-inflammatory cytokine/chemokine cascades that does not limit viral spread resulting in a predisposition to severe lung pathology. This response is similar to severe human respiratory paramyxovirus infections, which will serve as a model for the elucidation of hyper-immune inflammatory response that result to severe immunopathology in respiratory viral infections. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
  • Identifying a new locus that regulates the development of rete ovarian cysts in MRL/MpJ mice
    Shin-Hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yuka Namiki, Yasuhiro Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 59 (2-3) 79 - 88 0047-1917 2011/08 [Refereed][Not invited]
     
    MRL/MpJ (MRL) is a mouse model for autoimmune disease and develops ovarian cysts with age. The ovarian cysts originate from the rete ovarii, which is considered to be the remnant of fetal mesonephric tubules. In a previous study, we analyzed the genetic background of ovarian cysts by using backcross progenies between MRL and C57BL/6N (B6) mice. By interval mapping, suggestive linkages were detected on several chromosomes (Chrs), and a significant linkage on Chr 14 was designated as MRL Rete Ovarian Cyst (mroc). In the present study, which evaluated 113 F2 intercross progenies, a significant linkage appeared on Chr 6 at the marker position D6Mit188 (likelihood ratio statistic = 18.5). In particular, the peak regions of Chrs 6 and 14, which contain major causative loci by backcross analysis, showed close reverse interaction. From these results, a locus on Chr 6 was identified as mroc2, the second major locus associated with ovarian cyst formation in MRL mice.
  • Takahiro Seto, Evgeniy A. Tkachenko, Vyacheslav G. Morozov, Yoichi Tanikawa, Sergey I. Kolominov, Sergey N. Belov, Ichiro Nakamura, Nobuo Hashimoto, Yasuhiro Kon, Alexander E. Balakiev, Tamara K. Dzagurnova, Olga A. Medvedkina, Mina Nakauchi, Mariko Ishizuka, Kentaro Yoshii, Kumiko Yoshimatsu, Leonid V. Ivanov, Jiro Arikawa, Ikuo Takashima, Hiroaki Kariwa
    JOURNAL OF VIROLOGICAL METHODS 173 (1) 17 - 23 0166-0934 2011/04 [Not refereed][Not invited]
     
    Puumala virus (PUUV) and other Arvicolinae-borne hantaviruses are difficult to cultivate in cell culture. To isolate these hantaviruses efficiently, hantavirus nucleocapsid protein (NP)-positive but seronegative wild rodents were selected by NP-detection ELISA. Three of 68 Myodes glareolus captured in Samara, Russia, were NP-positive and seronegative. Syrian hamsters were inoculated with lung homogenates from NP-positive rodents for virus propagation. Virus isolation in vitro was carried out by inoculation of lung homogenates of NP-positive hamsters to Vero E6 cell monolayers. Two PUUV strains (Samara49/CG/2005 and Samara94/CG/2005) from M. glareolus were isolated in Vero E6 cells. Nucleotide and amino acid sequence identities of the S segment of these isolates to those of PUUV F-s808 from a fatal HFRS patient in Samara region were 96.7-99.3% and 99.3-100.0%, respectively. Morphologic features of Vero E6 cells infected with PUUV strain Samara49/CG/2005 were quite similar to those of Hantaan virus-infected cells. Isolation of Hokkaido virus from Myodes rufocanus captured in Hokkaido, Japan, was also performed. Hokkaido virus NP and RNA were recovered and maintained in hamsters. These results suggest that inoculation of Syrian hamsters with rodent samples is an efficient method for the isolation and maintenance of PUUV and other Arvicolinae-borne hantaviruses. (C) 2011 Elsevier B.V. All rights reserved.
  • Junpei Kimura, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    PLOS ONE 6 (1) e16472  1932-6203 2011/01 [Not refereed][Not invited]
     
    The kidney is a nonregenerative organ composed of numerous functional nephrons and collecting ducts (CDs). Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology. Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons. These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. We conclude that evaluation of urinary cellular patterns plays a key role in the early, noninvasive diagnosis of renal disease.
  • J. Vet. Med. Sci. 73 (5) 707 - 710 0916-7250 2011 [Not refereed][Not invited]
  • Takayuki Oishi, Shoichi Date, Yoko Shimamoto, Tomoko Saito, Keiko Hirota, Takeshi Sugaya, Yasuhiro Kon, Akiyoshi Fukamizu, Keiji Tanimoto
    JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION 30 (6) 484 - 492 1079-9893 2010/12 [Not refereed][Not invited]
     
    Angiotensinogen (AGT), mainly produced in the liver, is the precursor of angiotensin II, an important regulator of blood pressure and electrolyte homeostasis. We previously showed, in hepatoma-derived HepG2 cells that a hepatocyte nuclear factor 4 (HNF4) potentiated human AGT (hAGT) promoter activity and identified its binding sites (termed regions C and J) in the hAGT promoter region. We also showed in transgenic mouse (TgM) that the hAGT is abundantly expressed in the kidney where the level of endogenous mouse AGT (mAGT) expression is low. To elucidate molecular mechanisms of the AGT gene activation in the kidney, we first investigated the HNF4 and AGT expression in the mouse kidney. Northern blot, in situ hybridization and immunohistochemical analyses revealed that the hAGT and HNF4 were both expressed in the proximal tubular (PT) cells of the kidney. We then transfected the hAGT reporter constructs into immortalized mouse PT (mProx) cells and found that regions C and J contributed additively to the HNF4-potentiated hAGT promoter activity. Curiously, no obvious HNF4 binding motif was found in the corresponding region of the mAGT promoter and co-transfected HNF4 failed to activate this promoter in neither HepG2 nor mProx cells. These results suggest that the high-level hAGT expression in the TgM kidney is, at least in part, due to a presence of high-affinity HNF4 binding sites in its promoter.
  • Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abu Al Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shin-Hyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon
    VETERINARY RESEARCH COMMUNICATIONS 34 (6) 557 - 567 0165-7380 2010/08 [Not refereed][Not invited]
     
    Previously, the distribution of myoepithelial cells (mecs) in the salivary glands was studied by both immunohistochemistry, and transmission electron microscopy; however, little was elucidated concerning their morphological features, especially in goats. This study was performed to investigate the correlation between the cytoarchitecture of the mecs in goat major salivary glands (parotid, mandibular, and sublingual glands) and the nature of the saliva secretion. The cytoarchitectural features of the mecs were examined by scanning and transmission electron microscopy as well as immunohistochemically. The secretory endpieces in the parotid gland are of the pure serous type, but in both the mandibular and sublingual glands they are of the mixed type. In all studied glands, the intercalated ducts were covered by mecs which, unlike the large stellate cells that surrounded the secretory endpieces, were spindle-shaped with few cytoplasmic processes. Interestingly, the mecs were found to bulge on the basal surfaces of the serous acini and intercalated ducts in all glands and to be in close contact to the seromucous tubules surface in the mandibular and sublingual glands forming a continuous network around it. In conclusion, the differences in the degree of development of the mecs as well as the number of their cytoplasmic processes may be correlated with the nature of the secretion and the number of the secretory granules. Thus these observations may have some relevance in the diagnosis of atrophy and pathogenic conditions of these glands.
  • Masataka Chihara, Saori Otsuka, Osamu Ichii, Yoshiharu Hashimoto, Yasuhiro Kon
    MOLECULAR REPRODUCTION AND DEVELOPMENT 77 (7) 630 - 639 1040-452X 2010/07 [Not refereed][Not invited]
     
    The blood testis barrier (BTB) separates the seminiferous epithelium into the ad-luminal and basal compartments. During murine spermatogenesis, preleptotene/leptotene spermatocytes migrate from the basal to the adluminal compartment through the BTB during stages VIII-IX. In the present study, we focused on the tight junction (TJ) molecules and analyzed their spatiotemporal expression during the murine seminiferous epithelial cycle. Structural analysis revealed that the principal components of the BTB, for example, claudin-3, claudin-11, occludin, and zonula occludens-1 (ZO-1), were localized at the basal and luminal sides of the preleptotene/leptotene spermatocytes during the migration stages (VIII-IX). Although we detected claudin-11, occludin, and ZO-1 throughout spermatogenesis, claudin-3 was only detected during stages VI-IX. Quantitative PCR using dissected seminiferous tubules from three stages (Early: II-VI, Middle: VII-VIII, Late: IX-I) clarified that the mRNA levels of TJ molecules were not correlated with the histoplanimetrical protein levels during spermatogenesis. Additionally, tubulobulbar complexes, considered to be involved in the internalization of TJ, were observed at the BTB site. Furthermore, a significant reduction in the mRNA levels of genes for the degradation of occludin (Itch) and endocytic recycling (Rab13) were observed during the Late and Middle stages, respectively. Therefore, we hypothesized that the lag between mRNA and protein expression of TJ molecules may be due to posttranslational modulation, for example, tubulobulbar complexes and endocytic recycling processes. In conclusion, these findings indicate that the integrity of the BTB is maintained throughout spermatogenesis, and the stage-specific localization of claudin-3 protein plays an important role in regulating BTB permeability. Mol. Reprod. Dev. 77: 630-639, 2010. (C) 2010 Wiley-Liss, Inc.
  • O. Ichii, A. Kamikawa, S. Otsuka, Y. Hashimoto, N. Sasaki, D. Endoh, Y. Kon
    LUPUS 19 (8) 897 - 905 0961-2033 2010/07 [Not refereed][Not invited]
     
    B6. MRLc1(82-100) congenic mice carrying the telomeric region of lupus-prone MRL chromosome 1 develop autoimmune glomerulonephritis (GN). The GN susceptibility locus of B6. MRLc1(82-100) contains the interferon activated gene 200 (Ifi200) family, which consists of Ifi202, 203, 204, and 205. Recently, Ifi202 was suggested as a candidate gene for murine lupus. In this study, we assessed the association between Ifi200 family and GN in several disease models. We compared the expression of Ifi200 family members in 24 organs between the C57BL/6 and B6. MRLc1(82-100). The expressions of Ifi200 family members differed between strains, and the most dramatic differences appeared in Ifi202 expression. Briefly, in the blood, immune organs, lungs, and testes mRNA expression was higher in B6. MRLc1(82-100) mice. In the kidney and immune organs, only Ifi202 expression increased with the development of GN in B6. MRLc1(82-100), and significant differences from C57BL/6 were observed even before disease onset. Ifi202 expression in the kidneys of BXSB, NZB/WF1, and MRL/lpr was also significantly high in the early- and late-disease stages. Furthermore, laser microdissection-reverse-transcriptase-polymerase chain reaction analysis confirmed the high Ifi202 expression in all areas of B6. MRLc1(82-100) kidneys. In conclusion, in the Ifi200 family, Ifi202 expressions in the kidney and immune organs significantly increased with GN progression. Lupus (2010) 19, 897-905.
  • Tomonori Kanazawa, Akihiro Konno, Yoshiharu Hashimoto, Yasuhiro Kon
    DEVELOPMENTAL DYNAMICS 239 (4) 1145 - 1154 1058-8388 2010/04 [Not refereed][Not invited]
     
    Hepatocyte nuclear factor 4 alpha (Hnf4 alpha) is a transcription factor required for embryogenesis and organogenesis. In the adult kidney, Hnf4 alpha is expressed at a high level in proximal tubules. Although its expression begins from the embryonic period, its function in the developing kidney has remained almost unknown. In this study, we investigated the role of Hnf4 alpha in the cultured embryonic mouse kidney by gene silencing using the RNA interference method. Additionally, we identified the dynamics of Hnf4 alpha in the microenvironment of the developing kidney. As a result of gene silencing, the cellular organization in the condensed mesenchyme (CM) fell into disorder and many apoptotic cells appeared. In addition, laser microdissection-reverse transcriptase-polymerase chain reaction provided evidence that Hnf4 alpha gene expression began first in the CM. These results suggest the possibility that Hnf4 alpha plays an important role in the regulation of the cell survival at the CM stage in nephrogenesis. Developmental Dynamics 239:1145 1154, 2010. (C) 2010 Wiley-Liss, Inc.
  • Shin-hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    MAMMALIAN GENOME 21 (3-4) 162 - 171 0938-8990 2010/04 [Not refereed][Not invited]
     
    MRL/MpJ (MRL) is a model mouse for autoimmune diseases such as dermatitis, vasculitis, arthritis, and glomerulonephritis. In addition to these immune-associated disorders, we found that older MRL mice develop ovarian cysts originating from the rete ovarii, which is lined by ciliated or nonciliated epithelium and considered remnants of mesonephric tubules. Ovarian cysts, which are reported to have several sources, are associated with female infertility, but information regarding the genetic etiology of ovarian cysts originating from the rete ovarii is rare. In this study, to elucidate the genetic background of development of ovarian cysts, we performed quantitative trait locus (QTL) analysis using 120 microsatellite markers, which cover the whole genome of murine chromosomes, and 213 backcross progenies between female MRL and male C57BL/6N mice. The quantitative trait measured was the circumferences of rete ovarii or ovarian cysts. As a result, suggestive linkages were detected on Chrs 3, 4, 6, and 11, but significant linkages were located on Chr 14 by interval mapping. We thereby designated the 27.5-cM region of Chr 14 "MRL Rete Ovarian Cysts (mroc)." The peak regions of Chrs 4 and 14 in particular showed a close additive interaction (p < 0.00001). From these results we concluded that multiple loci on Chrs 3, 4, 6, 11, and 14 interact to result in development of ovarian cysts in MRL mice.
  • Saori Otsuka, Yuka Namiki, Osamu Ichii, Yoshiharu Hashimoto, Nobuya Sasaki, Daiji Endoh, Yasuhiro Kon
    MAMMALIAN GENOME 21 (3-4) 153 - 161 0938-8990 2010/04 [Not refereed][Not invited]
     
    MRL/MpJ (MRL) mouse testes have several unique characteristics, including the appearance of oocytes, the occurrence of metaphase-specific apoptosis of meiotic spermatocytes, and the presence of heat-shock-resistant spermatocytes. In the present study we used chromosomal mapping to determine the genomic background associated with small testis size in MRL mice. We prepared and analyzed C57BL/6-based congenic mice carrying MRL mouse loci. Quantitative trait loci (QTL) analysis revealed susceptibility loci for small testis size at 100 cM on chromosome (Chr) 1 and at around 80 cM on Chr 2. Analysis with B6.MRLc1 and B6.MRLc2 congenic mice and double-congenic mice confirmed the QTL data and showed that low testis weight in MRL mice was caused by germ cell apoptosis. Through histological examinations we found that B6.MRLc1 and B6.MRLc2 mice showed stage-specific apoptosis in their testes, the former at metaphase stage XII and the later at pachytene stage IV. Metaphase-specific apoptosis of spermatocytes occurs due to mutation of the exonuclease 1 (Exo1) gene located at 100 cM on Chr 1. Thus, the mutation of the Exo1 gene is also responsible for low testis weight caused by metaphase-specific apoptosis. In conclusion, testis weight is reduced in MRL mice due to apoptosis of germ cells caused by mutations in loci on Chrs 1 and 2.
  • Osamu Ichii, Saori Otsuka, Nobuya Sasaki, Akira Yabuki, Hiroshi Ohta, Mitsuyoshi Takiguchi, Yoshiharu Hashimoto, Daiji Endoh, Yasuhiro Kon
    LABORATORY INVESTIGATION 90 (3) 459 - 475 0023-6837 2010/03 [Not refereed][Not invited]
     
    Identification of factors that exacerbate a disease is important for the development of biomarkers. In this study, we discovered ectopic overexpression of interleukin-1 family, member-6 (IL-1F6) in several murine renal diseases. IL-1F6 participates in cytokine/chemokine production in the epithelium. In PCR array analysis for inflammatory mediators, Il1f6 showed the highest expression in the kidney of the B6. MRLc1 glomerulonephritis model. IL-1F6 was localized in the epithelium from the DCTs to CCDs, which showed tubular dilations or epithelial deciduations. Ultrastructual examination of the epithelial cells revealed that IL-1F6 was localized on the cytoplasmic ribosome, vesicles, and nucleus. In and around these tubules, we found infiltrations of CD3-positive T-cells and nestin- or alpha-smooth-muscle actin-positive mesenchymal cells. Expression of the IL-1F6 protein and Il1f6 mRNA in the kidney was increased by the development of TILs in the B6. MRLc1 model and in lupus (BXSB, NZB/WF1, and MRL/lpr), nephrotic syndrome (ICGN), and streptozotocin-induced diabetic models. IL-1F6 was also detected in the epithelia having squamous or deciduous contours in other organs such as the skin, esophagus, thymus, or uterus. In vitro analysis using M-1 cells from the murine collecting duct revealed that Il1f6 mRNA induction was related to the upregulation of IL-6, TGF-beta receptor-1, and mesenchymal markers and to the downregulation of epithelial markers and changes in the squamous cells of the epithelium. Interestingly, urine Il1f6 mRNA expression was detected earlier than renal dysfunctions in these mouse models. Ectopic overexpression of IL-1F6 in kidneys is associated with TILs and especially with cell infiltrations and changes in epithelial morphology. We propose that local overexpression of IL-1F6 is related to the development of TILs.
  • Jpn J Vet Res. 58 ((2)) 121 - 135 2010 [Not refereed][Not invited]
  • Akihiro Kamikawa, Osamu Ichii, Daisuke Yamaji, Takeshi Imao, Chihairu Suzuki, Yuko Okamatsu-Ogura, Akira Terao, Yasuhiro Kon, Kazuhiro Kimura
    DEVELOPMENTAL DYNAMICS 238 (5) 1092 - 1099 1058-8388 2009/05 [Not refereed][Not invited]
     
    Mammary glands develop postnatally in response to the hypothalamic-pituitary-gonadal axis. Obesity-induced changes in the local environment, however, retard mammary gland development during late pregnancy and lactation. To clarify the effects of obesity on fundamental duct development, we compared the mammary glands of nulliparous nonpregnant obese mice fed a high-fat diet with those of lean mice fed a normal diet. Obese mice had enlarged mammary glands, reflecting fat pad size, whereas the ducts in obese mice showed a less dense distribution with less frequent branching. Additionally, the ducts were surrounded by thick collagen layers, and were incompletely lined with myoepithelium. Because leptin receptors were localized in the epithelium region and leptin that was highly expressed in the obese glands suppressed mammary epithelial cell proliferation in vitro, the present results suggest that obesity disrupts mammary ductal development, possibly by remodeling the mammary microenvironment and promoting the expression of such paracrine factors as leptin. Developmental Dynamics 238:1092-1099, 2009. (C) 2009 Wiley-Liss, Inc.
  • Aki Ogura, Shigeru Oowada, Yasuhiro Kon, Aki Hirayama, Hironobu Yasui, Shunsuke Meike, Saori Kobayashi, Mikinori Kuwabara, Osamu Inanami
    CANCER LETTERS 277 (1) 64 - 71 0304-3835 2009/05 [Not refereed][Not invited]
     
    Mitochondria in mammalian cells are well-known to play an important role in the intrinsic pathway of genotoxic-agent-induced apoptosis by releasing cytochrome c into cytosol and to be a major source of reactive oxygen species (ROS). The aim of this study was to examine whether mitochondrial ROS are involved in radiation-induced apoptotic signaling in A549 cells. Post-irradiation treatment with N-acetyl-L-cystein (NAC) inhibited cytochrome c release from mitochondria but did not affect expression levels of Bcl-2, Bcl-X-L and Bax, suggesting that late production of ROS triggered cytochrome c release. Experiments using DCFDA (a classical ROS fluorescence probe) and MitoAR (a novel mitochondrial ROS probe) demonstrated that intracellular and mitochondrial ROS were enhanced 6 h after X irradiation. Furthermore, the O-2(-center dot) production ability of mitochondria isolated from A549 cells was evaluated by ESR spectroscopy combined with a spin-trapping reagent (CYPMPO). When isolated mitochondria were incubated with NADH, succinate and CYPMPO, an ESR spectrum due to CYPMPO-OOH was detected. This NADH/succinate-dependent O-2(-center dot) production from mitochondria of irradiated cells was significantly increased in comparison with that of unirradiated cells. These results indicate that ionizing radiation enhances O-2(-center dot), production from mitochondria to trigger cytochrome c release in A549 cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
  • O. Ichii, A. Konno, N. Sasaki, D. Endoh, Y. Hashimoto, Y. Kon
    LUPUS 18 (6) 491 - 500 0961-2033 2009/05 [Not refereed][Not invited]
     
    Female B6. MRLc1(82-100) congenic mice develop more severe autoimmune glomerulonephritis (AGN) than males. We assessed the effects of gonadectomy on the pathogenesis of AGN in these mice. One-month-old male and female mice were divided into sham-operated group (SG) and gonadectomized group (GG), and the pathological changes were investigated at 8 months. SG females showed higher spleen and thymus weights, serum total IgG and autoantibody levels, glomerular damage scores and percent IgG- and CD3-positive glomeruli as compared with SG males. Gonadectomy showed more remarkable effects in males than in females. Spleen and thymus weights, urinary albumin excretion, glomerular damage scores, percent IgG- and CD3-positive glomeruli, and CD3-positive areas in the spleen were significantly higher in GG males than in SG males. CD3-positive cells were observed in both the thymic cortex and medulla in all animals except SG males. The expression ratio of active Fc gamma receptor (Fcgr) 3 to inhibitory Fcgr2b in the kidneys, which we have previously demonstrated to have a great impact on pathogenesis in B6. MRLc1(82-100), was significantly higher in GG males than in SG males. These results suggested that the differences in the pathogenesis of AGN are primarily because of the inhibitory roles of the male sex hormones. Lupus (2009) 18, 491-500.
  • J. Vet. Med. Sci. 71 (9) 1161 - 1168 0916-7250 2009 [Not refereed][Not invited]
  • Jpn. J. Vet. Res. 57 (1) 3 - 11 2009 [Not refereed][Not invited]
  • Mina Nakauchi, Hiroaki Kariwa, Yasuhiro Kon, Kentaro Yoshii, Akihiko Maeda, Ikuo Takashima
    MICROBIOLOGY AND IMMUNOLOGY 52 (12) 625 - 630 0385-5600 2008/12 [Not refereed][Not invited]
     
    SARS-CoV has four major structural proteins: the N, S, M, and E proteins. To investigate the mechanism of SARS-CoV assembly, we cloned the genes encoding these four proteins into the eukaryotic expression vector pCAGGS and transfected them into 293T cells. When all four expression vectors were co-transfected VLP formed, as confirmed using electron microscopy. Using a rabbit polyclonal antibody specific to the N protein, N-protein-containing particles similar in size to the VLP were also observed by immunoelectron microscopy, indicating that the VLP contained the N protein. Co-immunoprecipitation analyses demonstrated an interaction between the N and M proteins, suggesting that N protein binds directly to M protein to be incorporated into VLP.
  • Osamu Ichii, Akihiro Konno, Nobuya Sasaki, Daiji Endoh, Yoshiharu Hashimoto, Yasuhiro Kon
    KIDNEY INTERNATIONAL 74 (3) 339 - 347 0085-2538 2008/08 [Not refereed][Not invited]
     
    Mag is an MRL-derived glomerulonephritis susceptibility locus that includes the Fcgr2b and Fcgr3 genes encoding the inhibitory Fc gamma receptor IIB (Fc gamma RIIB) and active Fc gamma RIII, respectively. We measured changes in gene balance in three B6.MRLc1 congenic mouse strains containing the 82-86, 92-100 and 100 cM regions of the MRL chromosome 1. We found that only the strain that has 92-100 (which includes Fcgr loci) developed glomerulonephritis. These congenic mice had splenomegaly, elevated blood urea nitrogen, anti-dsDNA antibodies and higher urinary albumin excretion compared to the parental strain C57BL/6(B6). Prior to the development of glomerulonephritis, large CD3- (T cell) and B220- (B cell) positive areas were identified in the spleens of B6. MRLc1(92-100) mice. Both Fc receptors were found in mesangial and dendritic cells; important sites of immune-complex clearance and antigen presentation. The Fc gamma RIII-positive areas were more prominent in the congenic strain. Fcgr2b mRNA was lower in the B6. MRLc1(92-100) kidney and spleen than in those organs of the B6 mice while Fcgr3 expression and the Fcgr3 to Fcgr2b mRNA ratio was higher in the congenic strain kidneys, spleen and thymus than in those of the B6 prior to and at an early stage of glomerulonephritis. We conclude that the imbalance of inhibitory and active Fc gamma receptors influences the pathogenesis of glomerulonephritis.
  • Saori Otsuka, Akihiro Konno, Yoshiharu Hashimoto, Nobuya Sasaki, Daiji Endoh, Yasuhiro Kon
    BIOLOGY OF REPRODUCTION 79 (1) 9 - 16 0006-3363 2008/07 [Not refereed][Not invited]
     
    Although mammals produce either sperm or eggs depending on their sex, we found oocytes in the testes of newborn MRL/MpJ male mice. In the present study, we report the morphological characteristics of testicular oocytes, the postnatal change of oocyte number per testis, and the expression of a few oocyte-specific genes in the testes of MRL/MpJ mice. The testicular oocytes had a diameter of 50-70 mu m and were surrounded by zonae pellucidae, which were observed between oocytes and follicular epithelial cells. Ultrastructurally, the testicular oocytes contained numerous microvilli and cortical granules, receiving cytoplasmic projections from follicular epithelial cells. The testicular oocytes appeared as early as at birth, and the largest number was found on Day 14. The testicular oocytes were detected in only MRL strains and B6MRLF1, but not in C57BL/6, C3H/He, BALB/c, DBA/2, A/J, and MRLB6F1. The expression of the oocyte-specific genes Zp1, Zp2, Zp3, and Omt2a was detected in testes from MRL/MpJ mice. These results suggest that newborn male MRL/Mpj mice with XY chromosomes can produce oocytes in their testes and that one of the genes causing this exists on the Y chromosome.
  • Autoimmune glomerulonephritis induced in congenic mouse strain carrying telomeric region of chromosome 1 derived from MRL/MpJ
    Osamu Ichii, Akihiro Konno, Nobuya Sasaki, Daiji Endoh, Yoshiharu Hashimoto, Yasuhiro Kon
    HISTOLOGY AND HISTOPATHOLOGY 23 (4) 411 - 422 0213-3911 2008/04 [Not refereed][Not invited]
     
    In lupus erythematosus-prone mice, including the BXSB, NZW and NZB strains, telomeric regions of chromosome 1 (Chr.1) contain major glomerulonephritis susceptibility loci such as Bxs3, Sle1, and Nba2. To assess whether strain MRL, a model for lupus erythematosus, had glomerulonephritis susceptibility loci on Chr.1, we created B6.MRLc1 (82-100) congenic mice carrying MRL/MpJ Chr.1 (82-100cM) based on the C57BL/6 background and investigated renal pathology. From 6 months of age, B6.MRLc1 (82-100) showed the onset of diseases such as splenomegaly due to proliferation of CD3-or B220-positive cells, glomerular damage, and an increased serum anti-dsDNA antibody concentration, and these were earlier and severer in females. The score for glomerular damage was higher in B6.MRLc1 (82-100) mice over 12 months old than in C57BL/6 or even in wild-type MRL/MpJ. Immune-complex depositions were demonstrated on glomerular basement membrane in B6.MRLc1 (82-100) by immunohistochemistry and electron microscopy. For the percentage of IgG1-positive glomeruli, B6.MRLc1 (82-100) had significantly higher values than C57BL/6. In evaluations of clinical parameters, serum levels of blood urea nitrogen and the anti-dsDNA antibody in B6.MRLc1 (82100) were significantly higher than those in C57BL/6. In conclusion, B6.MRLc1 (82-100) clearly developed autoimmune-mediated glomerulonephritis, and we demonstrated that MRL Chr.1 contained a novel glomerulonephritis susceptibility locus. We named this locus Mag (MRL autoimmune glomerulonephritis) and it provided new insights into the genetic basis and pathogenesis of lupus nephritis.
  • Saori Otsuka, Masatsugu Suzuki, Naoki Kamezak, Tatsuya Shima, Motoki Wakatsuki, Yasuhiro Kon, Noriyuki Ohtaishi
    JOURNAL OF EXPERIMENTAL ZOOLOGY PART A-ECOLOGICAL GENETICS AND PHYSIOLOGY 309A (3) 166 - 174 1932-5223 2008/03 [Not refereed][Not invited]
     
    Studies on the population dynamics of sea turtles require histological evaluation of the ontogenetic development and the activity of the gonads for reproduction. To investigate the growth-related changes of gonads in the immature male green turtle (Chelonia mydas), the histological changes of testes and epididymides and the localization of the androgen receptor, estrogen receptor alpha, estrogen receptor beta, and progesterone receptor were examined. The testes were categorized histologically into six developmental stages, and a scarce relationship between straight carapace length and gonadal development was confirmed based on the histological analysis. Several kinds of steroid hormone receptors were examined to show distributions in both testes and epididymides, for which their immunoreactivities were enhanced according to the developmental stage of the testes. These results suggest that straight carapace length is not an adequate indicator of maturity determination, whereas histological and immunohistochemical evaluations are useful in identifying the growth stages of green turtles, owing to the higher sensitivity to steroid hormones that appear during growth.
  • M. Z. I. Khan, S. H. Akter, M. N. Islam, M. R. Karim, M. R. Islam, Y. Kon
    ANATOMIA HISTOLOGIA EMBRYOLOGIA 37 (1) 52 - 59 0340-2096 2008/02 [Not refereed][Not invited]
     
    The present research has been designed to understand the effect of selenium and vitamin E on the lymphocyte and changes in the frequency of Ig-containing plasma cells in the lymphatic organ and ileum (representative organ for mucosa-associated lymphatic tissues) of different postnatal stages of Kasilla broiler chickens. A routine haematoxylin and eosin (H and E) stain were used to study the histology of the lymphocytic changes, and indirect immunoperoxidase staining method was performed for the study of the distributional and dynamical changes of the Ig-containing plasma cells within the lymphatic tissues and in the ileum of control broilers and in the broilers supplemented with different concentration of selenium and vitamin E in the diet. Histologically, the population of lymphocytes decreased in the lobules of the thymus, medulla of bursal follicles, splenic masses, lymphatic nodules of the cecal tonsil, and villi of the ilium in 0.1 mg and 0.5 mg selenium supplemented broilers in comparison with the control. The population of these cells was found to increase in 150 mg and 300 mg vitamin F supplemented chickens in the present study. In the spleen IgG- and the IgM-containing plasma cells were more than IgA-containing plasma cells. In contrast, in the cecal tonsil and ileum IgA-containing plasma cells were more than IgG- and IgM-containing plasma cells. The frequency of these immunopositive cells were decreased in 0.1 mg and 0.5 mg selenium supplementated chickens, and increased their frequency in the chickens supplemented with 150 mg and 300 mg vitamin E. In the spleen the frequency of IgM-containing plasma cells and both in the cecal tonsil and ileum, the IgG-containing plasma cells were more decreased by selenium supplementation which restored in their population by vitamin E supplementation.
  • Jpn. J. Vet. Res. 56 (3) 129 - 138 2008 [Not refereed][Not invited]
  • Expression of hepatic nuclear factor 4α in developing mice.
    Anat. Histol. Embryol. doi: 10.1111/j.1439-0264.2008.00889.x.  2008 [Not refereed][Not invited]
  • Akihiro Konno, Mitsuyoshi Takiguchi, Kensuke Takada, Takeshi Usami, Kaoru Azumi, Hisayo Kubota, Mutsumi Inaba, Junzo Saegusa, Yasuhiro Kon
    IMMUNOGENETICS 59 (11) 853 - 859 0093-7711 2007/11 [Not refereed][Not invited]
     
    Sjogren's syndrome (SS) is caused by an autoimmune sialodacryoadenitis, and up to 5% of patients with SS develop malignant B cell growth. The IQI mouse is a spontaneous model of primary SS in which B cells are the dominant cellular subpopulation among mononuclear infiltrates in sialitis lesions. Understanding the genetic control of aberrant B cell growth in IQI mice may help elucidate the genetic mechanisms involved in B-lineage hyperplasia leading to malignant transformation in human SS. B cell-dominant infiltration in the submandibular glands of 6-month-old IQI and C57BL/6 (B6) mice and their F1 and F2 progenies was quantified as B-lymphocytic sialitis score, and a genome-wide scan of 179 (IQI x B6) F2 females was performed to identify a quantitative trait locus (QTL) controlling this phenotype. A QTL significantly associated with variance in B-lymphocytic sialitis score was mapped to the D6Mit138 marker (position of 0.68cM) on proximal chromosome 6, with a logarithm of odds score of 4.3 (p=0.00005). This QTL, named autoimmune sialitis in IQI mice, associated locus 1 (Asq1), colocalized with Islet cell autoantigen 1 (Ica1), which encodes a target protein of the immune processes that define the pathogenesis of primary SS in humans and in the nonobese diabetic mouse model.
  • M. Z. I. Khan, M. R. Jahan, M. N. Islam, Z. Haque, M. R. Islam, Y. Kon
    TISSUE & CELL 39 (3) 141 - 149 0040-8166 2007/06 [Not refereed][Not invited]
     
    The distribution and frequency of immunoglobulin (Ig)-containing plasma cells, their variations due to sex, and the mode of secretion of Ig cells into the duct system of the Harderian gland was investigated in broiler and native chickens of both sexes in Bangladesh. The Harderian gland is covered by a capsule, and the connective tissue septa divide the gland into numerous unequal-sized numerous lobes and lobules. The Ig-containing plasma cells were located in the interstitial space, interacinar space, apical part of the lobule, and lumina of the lobules of the Harderian gland in both broiler and native chickens. The population of these Ig-containing plasma cells varied in between broiler and native chickens. and also between male and female broiler and native chickens. In the broiler, the number of IgM-containing plasma cells was higher; in contrast. in the native chickens, the population of IgA-containing plasma cells was larger. In the broiler, there were more IgA- and IgG-containing plasma cells in the male; in contrast, there were more IgM-containing plasma cells in female. In native chickens the frequency of IgA-containing plasma cells was greater in the female than male. When the data for broiler and native birds were compared, it was found that there were significantly more IgA- and IgG-containing plasma cells in the native male and female chickens than in the broiler males and females. The secretory Igs were located in the lumina of acini and the duct system of the Harderian gland. In the present study Ig-containing plasma cells were observed to be released in the lumina of the lobules of Harderian gland by the breakdown of acinar tissues in broilers, and by holocrine mode of secretion in the native chicken. These results suggested that the Harderian gland, even though it is not a lymphoid organ as a whole, but acts as an immunopotent organ in chickens, and that the gland in native chicken contains more Ig-containing plasma cells due to their scavening, (c) 2007 Elsevier Ltd. All rights reserved.
  • Y. Kon, A. Konno, Y. Hashimoto, D. Endoh
    ANATOMIA HISTOLOGIA EMBRYOLOGIA-JOURNAL OF VETERINARY MEDICINE SERIES C 36 (3) 172 - 178 0340-2096 2007/06 [Not refereed][Not invited]
     
    In MRL mice aged more than 1 year, but not in C57BL/6 mice, ovaries had grossly visible cysts presenting unilaterally or bilaterally. Postnatally, all MRL mice developed ovarian cysts by 8 months of age. Observations by light microscopy, including lectin histochemistry, indicated that the cysts sometimes included papillomatous tissues located at the hilar region and were similar to the rete ovarii system, but not to follicles. Two types of epithelial cells, ciliated and non-ciliated, were arranged on the cysts, in which both cell types had many microvilli projecting in various directions and random ramifications in the cystic lumen. These characteristics suggest that ovarian cysts developing in MRL mice originate mostly from the rete ovarii. Cysts derived from the rete ovarii at 8 months of age were histologically detected in all C3H mice as well as MRL mice, with variable incidence in ICR, AKR, CBA/N and ddY, and none in C57L/6, DBA/2, BALB and A/J mice. However, measurement of the maximum diameters of the ovarian cysts indicated that MRL mice regularly possessed the largest cysts visible to the naked eye. This is the first report of ovarian cysts in this inbred strain, suggesting that ovarian cysts in MRL mice appear with stable incidence and development.
  • Hironobu Yasui, Osamu Inanami, Taketoshi Asanuma, Daisuke Iizuka, Takayuki Nakajima, Yasuhiro Kon, Akira Matsuda, Mikinori Kumwabara
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 68 (1) 218 - 228 0360-3016 2007/05 [Not refereed][Not invited]
     
    Purpose: To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice. Methods and Materials: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis. Results: When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to these phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed. Conclusions: X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth. (c) 2007 Elsevier Inc.
  • Chem Biodivers. 4 (9) 2253 - 2267 2007 [Not refereed][Not invited]
     
    A new amphiphilic derivative, N-{[4-(lactobionamido)methyl]benzylidene}-1,1-dimethyl-2-(octylsulfanyl)ethylamine N-oxide, has a protective effect against copper-induced fulminant hepatitis in Long-Evans Cinnamon rats at an extremely low concentration compared with its original form alpha-phenyl-N-(tert-butyl) nitrone.
  • HAYASHI Masanobu, NISHIYA Hide, CHIBA Toshiaki, ENDOH Daiji, KON Yasuhiro, OKUI Toyo
    J. Vet. Med. Sci. 69 (2) 137 - 142 0916-7250 2007 [Not refereed][Not invited]
  • Junko Nio, Hiromi Takahashi-Iwanaga, Masami Morimatsu, Yasuhiro Kon, Toshihiko Iwanaga
    HISTOCHEMISTRY AND CELL BIOLOGY 126 (1) 45 - 56 0948-6143 2006/07 [Not refereed][Not invited]
     
    Galectin is an animal lectin that has high affinity to beta-galactoside of glycoconjugates. In the present study, cellular expression of galectin subtypes in the urinary system of adult mice was examined by in situ hybridization and immunohistochemistry. The major subtype expressed in the murine urinary system was galectin-3, which was expressed continuously from the kidney to the distal end of the urethra. The renal cortex expressed galectin-3 more intensely than the medulla. Renal galectin-3 immunoreactivity was strongest in the cortical collecting ducts, where principal cells were the sole cellular source. All cell layers of the transitional epithelium from the renal pelvis to the urethra strongly expressed galectin-3 at the mRNA and protein levels. An electron microscopic study demonstrated diffuse cytoplasmic localization of galectin-3 in principal cells of the collecting ducts and in the bladder epithelial cells. Urethral galectin-3 expression at the pars spongiosa decreased in intensity near the external urethral orifice, where the predominant subtype of galectin was substituted by galectin-7. The muscular layer of the ureter and urinary bladder contained significant signals for galectin-1. Taken together, the observations indicate that the adult urinary system shows intense and selective expression of galectin-3 in epithelia of the uretic bud- and cloaca-derivatives.
  • AR Cho, K Uchio-Yamada, T Torigai, T Miyamoto, Miyoshi, I, J Matsuda, T Kurosawa, Y Kon, A Asano, N Sasaki, T Agui
    MAMMALIAN GENOME 17 (5) 407 - 416 0938-8990 2006/05 [Not refereed][Not invited]
     
    The ICGN mouse is a model for nephrotic syndrome (NS) which presents with proteinuria, hyperlipidemia, and edema. In this study we attempted to identify the gene(s) responsible for NS. By analyzing albuminuria in 160 (ICGN x MSM)F-1 x ICGN backcross progenies, we found that NS in the ICGN mouse is caused by more than one gene. We then performed a quantitative trait locus (QTL) analysis and detected a QTL with a very high LOD score peak in the telomeric region of Chr 15. By analyzing the nucleotide sequence of 22 genes located close to the QTL, we found that the tensin2 gene of the ICGN mouse possessed an 8-nucleotide deletion mutation in exon 18, leading to a frameshift and giving rise to a terminal codon at a premature position. Analyses of in situ hybridization and immunohistochemistry revealed that tensin2 was expressed in podocytes and tubular epithelial cells in normal mice but not in the ICGN mouse. These data raise the possibility that a mutation of the tensin2 gene is responsible for NS of the ICGN mouse and tensin2 is a prerequisite for the normal kidney function.
  • D Yamaji, K Kimura, A Watanabe, Y Kon, T Iwanaga, MM Soliman, MM Ahmed, M Saito
    DOMESTIC ANIMAL ENDOCRINOLOGY 30 (3) 239 - 246 0739-7240 2006/03 [Not refereed][Not invited]
     
    Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic cytokine that plays a crucial role in the embryonic and postnatal development of various organs including the mammary gland. We cloned bovine HGF and its c-Met receptor cDNAs, and examined their expression during mammary gland development in dairy cows. The 2.5-kbp HGF cDNA clone contained a 2190 bp open reading frame coding a 730 amino acid protein, while the 4.8-kbp c-Met cDNA clone contained a 4152 bp open reading frame coding a 1384 amino acid protein. The bovine HGF and c-Met sequences exhibited more than 87% identity with those of other mammals. RT-PCR analysis revealed ubiquitous expression of both HGF and c-Met mRNAs in various bovine tissues tested. HGF mRNA was detected only in the inactive stage of bovine mammary gland development and not in the developing, lactating, and involuting stages, while c-Met mRNA was detected in the inactive and involuting stages. Immunohistochemical analysis demonstrated that the c-Met protein was found on mammary epithelial cells in the inactive, developing, and involuting stages, and on myoepithelial cells in all stages. These results suggest pivotal roles of HGF and c-Met in the development of bovine mammary gland. (c) 2005 Elsevier Inc. All rights reserved.
  • J Nio, Y Kon, T Iwanaga
    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY 53 (11) 1323 - 1334 0022-1554 2005/11 [Not refereed][Not invited]
     
    Galectin is an animal lectin that recognizes beta-galactosides of glycoconjugates and is abundant in the gut. This study revealed the cellular expression of galectin subtypes throughout the mouse digestive tract by in situ hybridization. Signals for five subtypes (galectin-2, -3, -4/6, and -7) were detected exclusively in the epithelia. In the glandular stomach, galectin-2 and -4/6 were predominantly expressed from gastric pits to neck of gastric glands, where mucous cells were the main cellular sources. The small intestine exhibited intense, maturation-associated expressions of galectin-2, -3, and -4/6 mRNAs. Galectin-2 was intensely expressed from crypts to the base of villi, whereas transcripts of galectin-3 gathered at villous tips. Signals for galectin-4/6 were most intense at the lower half of villi. Galectin-2 was also expressed in goblet cells of the small intestine but not in those of the large intestine. In the large intestine, galectin-4/6 predominated, and the upper half of crypts simultaneously contained transcripts of galectin-3. Stratified epithelium from the lip to forestomach and anus intensely expressed galectin-7 with weak expressions of galectin-3. Because galectins in the digestive tract may be multi-functional, information on their cell/ stage-specific expression contributes to a better understanding of the functions and pathological involvements of galectins.
  • Morpho-genetic investigation of metaphase-specific cell death in meiotic spermatocytes in mice.
    Anat. Sci. Int., 80 141 - 152 2005 [Not refereed][Not invited]
  • J. Interferon Cyokine Res. 25 169 - 273 2005 [Not refereed][Not invited]
  • Upregulation of renal renin-angiotensin system in mouse diabetic nephropathy.
    Jpn. J. Vet. Res. 53 (1-2) 13 - 26 2005 [Not refereed][Not invited]
  • Mammal. Genome 16 (2) 96 - 102 2005 [Not refereed][Not invited]
  • D Endoh, T Mizutani, R Kirisawa, Y Maki, H Saito, Y Kon, S Morikawa, M Hayashi
    NUCLEIC ACIDS RESEARCH 33 (6) e65  0305-1048 2005 [Not refereed][Not invited]
     
    A method for the isolation of genomic fragments of RNA virus based on cDNA representational difference analysis (cDNA RDA) was developed. cDNA RDA has been applied for the subtraction of poly(A)(+) RNAs but not for poly(A)(-) RNAs, such as RNA virus genomes, owing to the vast quantity of ribosomal RNAs. We constructed primers for inefficient reverse transcription of ribosomal sequences based on the distribution analysis of hexanucleotide patterns in ribosomal RNA. The analysis revealed that distributions of hexanucleotide patterns in ribosomal RNA and virus genome were different. We constructed 96 hexanucleotides (non-ribosomal hexanucleotides) and used them as mixed primers for reverse transcription of cDNA RDA. A synchronous analysis of hexanucleotide patterns in known viral sequences showed that all the known genomic-size viral sequences include non-ribosomal hexanucleotides. In a model experiment, when non-ribosomal hexanucleotides were used as primers, in vitro transcribed plasmid RNA was efficiently reverse transcribed when compared with ribosomal RNA of rat cells. Using non-ribosomal primers, the cDNA fragments of severe acute respiratory syndrome coronavirus and bovine parainfluenza virus 3 were efficiently amplified by subtracting the cDNA amplicons derived from uninfected cells from those that were derived from virus-infected cells. The results suggest that cDNA RDA with non-ribosomal primers can be used for species-independent detection of viruses, including new viruses.
  • Transgenic co-placement strategy reveals a cell-type dependent role for direct repeat sequences in human angiotensinogen gene transcription in BAC transgenic mice.
    Mol. Cell. Biol. 25 (8) 2938 - 2945 2005 [Not refereed][Not invited]
  • HAYASHI Masanobu, MIYANE Kazuhiro, SENOU Misato, ENDOH Daiji, HIGUCHI Hidetoshi, NAGAHATA Hajime, NAKAYAMA Kenji, KON Yasuhiro, OKUI Toyo
    Exp. Anim. 54 (5) 403 - 412 1341-1357 2005 [Not refereed][Not invited]
  • M Hayashi, K Miyane, T Hirooka, D Endoh, H Higuchi, H Nagahata, K Nakayama, Y Kon, T Okui
    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS 1674 (3) 312 - 318 0304-4165 2004/11 [Not refereed][Not invited]
     
    Effects of treatment with trientine, a specific copper-chelating agent, on accumulation of copper and induction of DNA strand breaks were investigated in Long-Evans Cinnamon (LEC) rats, an animal model for human Wilson's disease. Copper accumulated in the livers of LEC rats in an age-dependent manner from 4 to 13 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, hepatic copper contents did not increase and were maintained at the same levels as those in 10-week-old LEC rats. When the amounts of DNA single-strand breaks (SSBs) were estimated by a comet assay, SSBs of DNA were induced in a substantial population of LEC rat hepatic cells around 8 weeks of age and the amounts of SSBs increased in an age-dependent manner from 8 to 15 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, the observed number of cells with DNA damage decreased dramatically, suggesting that induction of SSBs of DNA was inhibited and/or SSBs were repaired during the period of treatment with trientine. The results show that treatment of LEC rats with trientine decreases the number of DNA strand breaks observed, although copper contents remain high in the liver. (C) 2004 Elsevier B.V All rights reserved.
  • J Nio, W Fujimoto, A Konno, Y Kon, M Owhashi, T Iwanaga
    HISTOCHEMISTRY AND CELL BIOLOGY 121 (6) 473 - 482 0948-6143 2004/06 [Not refereed][Not invited]
     
    Ym is one of the chitinase family proteins, which are widely distributed in mammalian bodies and can bind glycosaminoglycans such as heparin/heparan sulfate. Ym1 is a macrophage protein produced in parasitic infections, while its isoform, Ym2, is upregulated in lung under allergic conditions. In the present study, we revealed the distinct cellular expression of Ym1 and Ym2 in normal mice by in situ hybridization and immunohistochemistry. Ym1 was principally expressed in the lung, spleen, and bone marrow, while Ym2 was found in the stomach. Ym1-expressing cells in the lung were alveolar macrophages, and the immunoreactivity for Ym1 was localized in rough endoplasmic reticulum. In the spleen, Ym1-expressing cells gathered in the red pulp and were electron microscopically identified as immature neutrophils. In the bone marrow, immature neutrophils were intensely immunoreactive, but lost this immunoreactivity with maturation. Moreover, needle-shaped crystals in the cytoplasm of macrophages, which formed erythroblastic islands, also showed intense Ym1 immunoreactivity. Ym2 expression was restricted to the stratified squamous epithelium in the junctional region between forestomach and glandular stomach. The function of Ym1 and Ym2 is still unclear; however, the distinct cellular localization under normal conditions suggests their important roles in hematopoiesis, tissue remodeling, or immune responses as an endogenous lectin.
  • T Asanuma, O Inanami, K Tabu, K Waki, Y Kon, M Kuwabara
    NEUROSCIENCE LETTERS 359 (1-2) 57 - 60 0304-3940 2004/04 [Not refereed][Not invited]
     
    The present experiments were carried out to provide direct in vivo evidence for the involvement of c-Jun N-terminal kinase (JNK) in the induction of ischemic brain injury. Malonate, which produces lesions similar to those of focal ischemia-reperfusion by a reversible inhibition of succinate dehydrogenase in mitochondria, was injected into the left striatum in the rat brain without or with the simultaneous injection of a cell permeable peptidic JNK inhibitor, (L)-HIV-TAT(48-57)-PP-JP-JBD(20). Two regions of malonate-induced brain injury were visualized as a hyperintense region with surrounding hypointense regions by apparent diffusion coefficient mapping magnetic resonance imaging. The INK inhibitor significantly counteracted both hyper- and hypointense regions at the early stage of brain injury. Histological examination clarified that the inhibitor suppressed the induction of coagulation necrosis and spongy degeneration at early and late stages. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
  • Strain difference of spermatogenesis in cryptorchid testis in mice.
    Comp. Med. 54 (2) 179 - 184 2004 [Not refereed][Not invited]
  • Hashimoto, Y., Sadamoto, Y., Konno, A., Kon, Y. and Iwanaga, T. : Distribution of neutral amino acid transporter ASCT1 in the non-neuronal tissues of mice. Jpn. J. Vet. Res., 52(3), 113-124.*
    2004 [Not refereed][Not invited]
  • Namiki, Y., Kon, Y., Sasaki, N., Agui, T. and Endoh, D. : Exon skipping of exonuclease 1 in MRL/MpJ mice is caused by a nucleotide substitution of the branchpoint sequence in intron eight. Jpn. J. Vet. Res., 52(3), 125-134.*
    2004 [Not refereed][Not invited]
  • Saito, T., Ishida, J., Takimoto-Ohnishi, E., Takamine, S., Shimizu, K., Sugaya, T., Kato, H., Matsuoka T., Nangaku, M., Kon, Y., Sugiyama, F., Yagami, K. and Fukamizu, A. : An essential role for angiotensin II type 1a receptor in pregnancy-associated h・・・
    2004 [Not refereed][Not invited]
     
    Saito, T., Ishida, J., Takimoto-Ohnishi, E., Takamine, S., Shimizu, K., Sugaya, T., Kato, H., Matsuoka T., Nangaku, M., Kon, Y., Sugiyama, F., Yagami, K. and Fukamizu, A. : An essential role for angiotensin II type 1a receptor in pregnancy-associated hypertension with intrauterine growth retardation. FASEB J., 18(2), 388-90.*
  • Asano, A., Kon, Y. and Agui, T. : The mRNA regulation of porcine double-stranded RNA-activated protein kinase gene. J. Vet. Med. Sci., 66(12), 1523-1528.*
    2004 [Not refereed][Not invited]
  • INANAMI O, IIZUKA D, IWAHARA A, YAMAMORI T, KON Y, ASANUMA T, MATSUDA A, KASHIWAKURA I, KITAZATO K
    Rad. Res. 162 (6) 635 - 645 0033-7587 2004 [Not refereed][Not invited]
  • Characterization of the Chicken PKR: Polymorphism of the gene and Antiviral Activity against Vesicular Stomatitis Virus.
    Jpn. J. Vet. Res. 51 (3-4) 123 - 134 2004 [Not refereed][Not invited]
  • Kariwa, H., Tanabe, H., Mizutani, T., Kon, Y., Lokugamage, K., Lokugamage, N., Iwasa, M. A., Hagiya, T., Araki, K., Yoshimatsu, K., Arikawa, J. and Takashima, I. (2003): Synthesis of Seoul virus RNA and structural proteins in cultured cells. Arch. Viro・・・
    2003 [Not refereed][Not invited]
     
    Kariwa, H., Tanabe, H., Mizutani, T., Kon, Y., Lokugamage, K., Lokugamage, N., Iwasa, M. A., Hagiya, T., Araki, K., Yoshimatsu, K., Arikawa, J. and Takashima, I. (2003): Synthesis of Seoul virus RNA and structural proteins in cultured cells. Arch. Virol., 148, 1671-1685.*
  • Namiki, Y., Endoh, D. and Kon, Y. (2003): Genetic mutation associated with meiotic metaphase-specific apoptosis in MRL/MpJ mice. Mol. Reprod. Dev., 64, 179-188.*
    2003 [Not refereed][Not invited]
  • Saito, T., Ishida, J., Takimoto-Ohnishi, E., Takamine, S., Shimizu, K., Sugaya, T., Kato, H., Matsuoka T., Nangaku, M., Kon, Y., Sugiyama, F., Yagami, K. and Fukamizu, A. (2003): An essential role for angiotensin II type 1a receptor in pregnancy-associ・・・
    2003 [Not refereed][Not invited]
     
    Saito, T., Ishida, J., Takimoto-Ohnishi, E., Takamine, S., Shimizu, K., Sugaya, T., Kato, H., Matsuoka T., Nangaku, M., Kon, Y., Sugiyama, F., Yagami, K. and Fukamizu, A. (2003): An essential role for angiotensin II type 1a receptor in pregnancy-associated hypertension with intrauterine growth retardation. FASEB J., (on line).*
  • Okamura, T., Miyoshi, I., Takahashi, K., Mototani, Y., Ishigaki, S., Kon, Y. and Kasai, N. (2003): Bilateral congenital cataracts results from a gain-of-function mutation in the gene for aquaporin-0 in mice. Genomics, 81(4), 361-368.*
    2003 [Not refereed][Not invited]
  • Kitamura, G., Ohta, T., Kai, T., Kon, Y. and Ito, S. (2002): "Inhibitory effects of opioids on voltage-dependent Ca2+ channels and catecholamine secretion in cultured porcine adrenal chromaffin cells." Brain Res., 942(1-2), 11-22.*
    2002 [Not refereed][Not invited]
  • Asanuma, T., Ishibashi, H., Konno, A., Kon, Y., Inanami, O. and Kuwabara, M. (2002): "Assessment of neuroprotective ability of a spin trap, a-phenyl-N-tert-butylnitrone, against malonate-induced ischemic injury of rat brain by apparent water diffusion ・・・
    2002 [Not refereed][Not invited]
     
    Asanuma, T., Ishibashi, H., Konno, A., Kon, Y., Inanami, O. and Kuwabara, M. (2002): "Assessment of neuroprotective ability of a spin trap, a-phenyl-N-tert-butylnitrone, against malonate-induced ischemic injury of rat brain by apparent water diffusion coefficient mapping. Neurosci." Lett., 329, 281-284.*
  • Miyoshi, I., Takahashi, K., Kon, Y., Okamura, T., Mototani, Y., Araki, Y. and Kasai, N. (2002): "Mouse transgenic for murine oviduct-specific glycoprotein promoter-driven Simian Virus 40 large-T antigen: Tumor formation and its hormonal regulation." Mo・・・
    2002 [Not refereed][Not invited]
     
    Miyoshi, I., Takahashi, K., Kon, Y., Okamura, T., Mototani, Y., Araki, Y. and Kasai, N. (2002): "Mouse transgenic for murine oviduct-specific glycoprotein promoter-driven Simian Virus 40 large-T antigen: Tumor formation and its hormonal regulation." Mol. Reprod. Dev., 63, 168-176.*
  • Kon, Y., Namiki, Y. and Endoh, D. (2002): "Expression and distribution of inducible nitric oxide synthase in mouse testis." Jpn. J. Vet. Res., 50(2-3).*
    2002 [Not refereed][Not invited]
  • Mori, K., Kon, Y., Konno, A. and Iwanaga, T.: "Cellular Distribution of Napsin (Kidney-derived Aspartic Protease-like Protein, KAP) mRNA in the Kidney, Lung and Lymphatic Organs of Adult and Developing Mice", Archaevs Histology and Cytology,64:319-327(・・・
    2001 [Not refereed][Not invited]
     
    Mori, K., Kon, Y., Konno, A. and Iwanaga, T.: "Cellular Distribution of Napsin (Kidney-derived Aspartic Protease-like Protein, KAP) mRNA in the Kidney, Lung and Lymphatic Organs of Adult and Developing Mice", Archaevs Histology and Cytology,64:319-327(2001)*
  • 2001 [Not refereed][Not invited]
     
    Miyoshi, I., Maki, K., Kon, Y., Yamashita, T., Aoyama, S., Hayashizaki, Y. and Kasai, N.: "Targeting oncogenesis by introduction of a 5.2-Kbp segment of the 5ユ regulatory region of the human thyrotropin b-subunit gene", Endocrine Research,27:387-398(2001)*
  • Takada, G., Jin, M. B., Masuko, H., Yamashita, K., Kitagawa, N., Takeda, K,. Sakurai, N., Kon, Y., Horiuchi, H., Shimamura, T., Furukawa, H. and Todo S.: "Role of local renin-angiotensin system in warm ischemia and reperfusion injury of the liver" Tran・・・
    2001 [Not refereed][Not invited]
     
    Takada, G., Jin, M. B., Masuko, H., Yamashita, K., Kitagawa, N., Takeda, K,. Sakurai, N., Kon, Y., Horiuchi, H., Shimamura, T., Furukawa, H. and Todo S.: "Role of local renin-angiotensin system in warm ischemia and reperfusion injury of the liver" Transplantion Procceeding,33:824-825(2001)*
  • Asanuma, T., Ohkura, K., Yamamoto, T, Kon, Y., Shimokawa, S. and Kuwabara, M.: "Three-dimensional magnetic resonance imaging of lung and liver tumors in mice by use of transversal multislice magnetic resonance images", Comparative Medicine,51:138-144(2・・・
    2001 [Not refereed][Not invited]
     
    Asanuma, T., Ohkura, K., Yamamoto, T, Kon, Y., Shimokawa, S. and Kuwabara, M.: "Three-dimensional magnetic resonance imaging of lung and liver tumors in mice by use of transversal multislice magnetic resonance images", Comparative Medicine,51:138-144(2001)*
  • Kiba, T., Saito, S., Numata, K., Kon, Y., Mizutani, T. and Sekihara, H.: "Expression of apoptosis on rat liver by hepatic vagus hyperactivity after ventromedial hypothalamic lesioning", American Journal of Physiology: Gastrointestinal and Liver Physio・・・
    2001 [Not refereed][Not invited]
     
    Kiba, T., Saito, S., Numata, K., Kon, Y., Mizutani, T. and Sekihara, H.: "Expression of apoptosis on rat liver by hepatic vagus hyperactivity after ventromedial hypothalamic lesioning", American Journal of Physiology: Gastrointestinal and Liver Physiology,280:G958-G967(2001).*
  • Ohuchi, J., Arai, T., Kon, Y., Asano, A., Yamauchi, H. and Watanabe, T.: "Characterization of a novel gene, sperm-tail-associated protein (Stap), in mouse post-meiotic testicular germ cells", Molelucar Reproduction and Development,59:350-358(2001)*
    2001 [Not refereed][Not invited]
  • Kon, Y. and Endoh, D.: "Heat-shock resistance in experimental cryptorchid testis of mice", Molecular Reproduction and Development, 58:216-222(2001)*
    2001 [Not refereed][Not invited]
  • Seo, K. W., Kon,Y. and Watanabe,T. "Embryonic hematopoiesis defect in the Tattered-hokkaido (Tdho) mouse." Lab. Anim. Sci., 50(1), 8-12, (2000)*
    2000 [Not refereed][Not invited]
  • Yanai, K., Saito, T., Kakinuma, Y., Kon, Y., Hirota, K., Taniguchi-Yanai, K., Nishijo, N., Shigematsu, Y., Horiguchi, H., Kasuya, Y., Sugiyama, F., Yagami, K., Murakami, K. and Fukamizu, A. "Renin-dependent cardiovascular functions and renin-independen・・・
    2000 [Not refereed][Not invited]
     
    Yanai, K., Saito, T., Kakinuma, Y., Kon, Y., Hirota, K., Taniguchi-Yanai, K., Nishijo, N., Shigematsu, Y., Horiguchi, H., Kasuya, Y., Sugiyama, F., Yagami, K., Murakami, K. and Fukamizu, A. "Renin-dependent cardiovascular functions and renin-independent blood-brain barrier functions revealed by renin-deficient mice." J. Biol. Chem., 275(1), 5-8, (2000)*
  • Okamura, T., Gotoh, M., Kon, Y., Imai, Y., Yamamoto, M. and Watanabe, T. "Molecular cloning and characterization of mouse testis poly(A) binding protein II encoded by Pabp3 gene which transcomponents a meiotic mutant sme2 of S. pombe." Biochem. Genet.,・・・
    2000 [Not refereed][Not invited]
     
    Okamura, T., Gotoh, M., Kon, Y., Imai, Y., Yamamoto, M. and Watanabe, T. "Molecular cloning and characterization of mouse testis poly(A) binding protein II encoded by Pabp3 gene which transcomponents a meiotic mutant sme2 of S. pombe." Biochem. Genet., 38(1-2), 1-11, (2000)*
  • Kon, Y. and Endoh, D. "Morphological study of metaphase-specific apoptosis in MRL mouse testis." Anat. Histol. Embryol., 29(5), 313-319, (2000)*
    2000 [Not refereed][Not invited]
  • Endoh, D., Cho, K. O., Tsukamoto, K., Morimura, T., Kon, Y. and Hayashi, M. "Application of representational differential analysis to genomic fragments of Marekユs disease virus." J. Clin. Microbiol., 38(12), 4310-4314, (2000)*
    2000 [Not refereed][Not invited]
  • Jin, H.-K., Takada, A., Kon, Y., Haller, O. and Watanabe, T. "Identification of the murine Mx2 gene: Interferon-induced expression of the Mx2 protein from the feral mouse gene confers resistance to vesicular stomatitis virus", J. Virol., 73(6): 4925-49・・・
    1999 [Not refereed][Not invited]
     
    Jin, H.-K., Takada, A., Kon, Y., Haller, O. and Watanabe, T. "Identification of the murine Mx2 gene: Interferon-induced expression of the Mx2 protein from the feral mouse gene confers resistance to vesicular stomatitis virus", J. Virol., 73(6): 4925-4930 (1999)
  • Kon, Y., Endoh, D. and Iwanaga, T. "Expression of protein gene product 9.5, a neuronal ubiquitin C-terminal hydrolase, and its developing change in Sertoli cells of mouse testis", Mol. Reprod. Dev., 54(4): 333-341 (1999)
    1999 [Not refereed][Not invited]
  • Khlood, E. B. M., Miyoshi, H., Iwata, H., Kazusaka, A., Kon, Y., Hadid, A. H. A., Moustafe, E. K., Ghonim, M. H. and Fijita, S. "Effects of concurrent exposure to 3-methylcholanthrene and vitamin A on fetal development in rats", Jpn. J. Vet. Res., 47(1・・・
    1999 [Not refereed][Not invited]
     
    Khlood, E. B. M., Miyoshi, H., Iwata, H., Kazusaka, A., Kon, Y., Hadid, A. H. A., Moustafe, E. K., Ghonim, M. H. and Fijita, S. "Effects of concurrent exposure to 3-methylcholanthrene and vitamin A on fetal development in rats", Jpn. J. Vet. Res., 47(1-2): 13-23 (1999)
  • Kon, Y. and Endoh, D. "Renin in exocrine glands of variable mouse strains", Anat. Histol. Embryol., 28(4): 239-242 (1999)
    1999 [Not refereed][Not invited]
  • Kon, Y., Horikoshi, H. and Endoh, D. "Metaphase-specific cell death in meiotic spermatocytes in mice", Cell Tissue Res., 296(2): 359-369 (1999)
    1999 [Not refereed][Not invited]
  • Kon, Y. and Endoh, D. "Expression of angiotensinogen in the uterus induced by coagulating gland renin in mice", Anat. Histol. Embryol., 28(2): 119-124 (1999)
    1999 [Not refereed][Not invited]
  • Ishida, J. , Asada, S., Daitoku, H., Fujiwara, K., Kon, Y., Sugaya, T., Murakami, K., Nakajima, T., Kasuya, Y. and Fukamizu, A. "Expression and characterization of mouse angiotensin II type 1a receptor tagging hemagglutinin epitope in cultured cells", ・・・
    1999 [Not refereed][Not invited]
     
    Ishida, J. , Asada, S., Daitoku, H., Fujiwara, K., Kon, Y., Sugaya, T., Murakami, K., Nakajima, T., Kasuya, Y. and Fukamizu, A. "Expression and characterization of mouse angiotensin II type 1a receptor tagging hemagglutinin epitope in cultured cells", Int. J. Mol. Med., 3(3): 263-270 (1999)
  • Asanuma, T., Shimokawa, S., Inanami, O, Kon, Y. and Kuwabara, M.: "Visualization of the topographical structure of the anesthetized mouse brain by MR microimaging." Journal of Veterinary Medical Science, 60:1311-1314(1998)
    1998 [Not refereed][Not invited]
  • 1998 [Not refereed][Not invited]
     
    Ui, M., Endoh, D., Cho, K.-O., Kom, Y., Iwata, A., Maki, Y., Sato, F. and Kuwabara, M.: "Transcriptional analysis of Merek's disease virus (MDV) genes in MDV-transformed lymphoblastoid cell lines without MDV-activated cells." Journal of Veterinary Medical Science, 60:823-829(1998)*
  • 1998 [Not refereed][Not invited]
     
    Endoh, D., Ito, M., Cho, K.-O., Kon, Y., Morimura, T., Hayashi, M. and Kuwabara, M.: "Retroviral sequence located in border region of short unique region and short terminal repeat of Md5 strain of Marek's disease virus type1.", Journal of Veterinary Medical Science, 60:227-235(1998)*
  • Kon, Y., Endoh, D., Yamashita, T., and Watanabe, T.: "Expression of renin in the rat liver." Anatomia Histologia Embryologia, 27:111-118(1998)*
    1998 [Not refereed][Not invited]
  • Kon, Y., Miyoshi, M. and Hashimoto, Y.: "Chemoreceptive epithelioid cells in the chicken aorta. An electron microscopical study." Anatomia Histologia Embryologia, 27:161-166(1998)*
    1998 [Not refereed][Not invited]
  • 1997 [Not refereed][Not invited]
     
    Maeda, A., Kon, Y., Watanabe, T. and Hayashi, M. : "Resistance to infection with mouse hepatitis virus (MHV) in the cell clones derived from persistently infected DBT cells with the JHM strain of MHV", Journal of Veterinary Medical Science, 59 : 545-549 (1997)*
  • Yamashita, T., Yamazaki, H., Kon, Y., Watanabe, T., Arikawa, J., Miyoshi, I., Kasai, N. and Kuwabara, M. : "Progressive effect of α-phenyl-N-tert-butyl nitrone (PBN) on rat embryo development in vitro", Free Radical Biology and Medicine, 23 : 1073-1077・・・
    1997 [Not refereed][Not invited]
     
    Yamashita, T., Yamazaki, H., Kon, Y., Watanabe, T., Arikawa, J., Miyoshi, I., Kasai, N. and Kuwabara, M. : "Progressive effect of α-phenyl-N-tert-butyl nitrone (PBN) on rat embryo development in vitro", Free Radical Biology and Medicine, 23 : 1073-1077 (1997)*
  • Kon, Y., Miyoshi, I., Maki, K., Yamashita, T., Aoyama, S., Watanabe, T., Hayashizaki, Y. and Kasai, N. : "Morphological study of pituitary tumorigenesis in transgenic mice induced by tryrotropin β-subunit and Simian virus 40 large T-antigen hybrid onco・・・
    1997 [Not refereed][Not invited]
     
    Kon, Y., Miyoshi, I., Maki, K., Yamashita, T., Aoyama, S., Watanabe, T., Hayashizaki, Y. and Kasai, N. : "Morphological study of pituitary tumorigenesis in transgenic mice induced by tryrotropin β-subunit and Simian virus 40 large T-antigen hybrid oncogene", Histology and Histopathology, 12 : 981-990 (1997)*
  • Asanuma, T., Hirano, Y., Ohkura, K., Kon, Y., Shimokawa, S., Kasai, N. and Muwabara, M. : "Magnetic resonance imaging of hepatocellular carcinona in Long-Evans Cinnamon rats under a magnetic field of 7.05 T", Japanese Journal of Veterinary Research, 45・・・
    1997 [Not refereed][Not invited]
     
    Asanuma, T., Hirano, Y., Ohkura, K., Kon, Y., Shimokawa, S., Kasai, N. and Muwabara, M. : "Magnetic resonance imaging of hepatocellular carcinona in Long-Evans Cinnamon rats under a magnetic field of 7.05 T", Japanese Journal of Veterinary Research, 45 : 147-151 (1997)*
  • Y. Kon, D. Endoh, A. Fukamizu, K. Murakami, T. Yamashita and T. Watanabe : "Detection of coagulating gland renin by hybridohistochemistry", Anatomia Histologia Embryologia, 25 : 289-294 (1996)*
    1996 [Not refereed][Not invited]
  • J. -H. Lee, Y. Hashimoto, Y. Kon, M. Sugimura and H. -S. Lee : "Immunoelectron microscopic study on the endocrine pancreas of the native Korean goat", Korean Journal of Electron Microscopy, 26 : 67-77 (1996)*
    1996 [Not refereed][Not invited]
  • H. I. Ismail, Y. Hashimoto, Y. Kon, K. Okada, W. C. Davis and T. Iwanaga : "Lymphocyte subpopulations in the mammary gland of the goat", Veteterinary Immunology and Immunopathology, 52 : 201-212 (1996)*
    1996 [Not refereed][Not invited]
  • M. Z. I. Kahn, Y. Hashimoto, A. Konno, Y. Kon and T. Iwanaga : "Development of T-lymphocyte subpopulations in the postnatal chicken oviduct", Cell and Tissue Research, 284 : 317-325 (1996)*
    1996 [Not refereed][Not invited]
  • M. Hayashi, F. Okada, K. Ishida, A. Maeda, Y. Kon, T. Mizutani, T. Itoh, S. Arai and T. Watanabe :"Cytolytic activity induced by intramuscular injection of plasmid DNA expressing the nucleocapsid protein of the JHM strain of mouse hepatitis virus into ・・・
    1996 [Not refereed][Not invited]
     
    M. Hayashi, F. Okada, K. Ishida, A. Maeda, Y. Kon, T. Mizutani, T. Itoh, S. Arai and T. Watanabe :"Cytolytic activity induced by intramuscular injection of plasmid DNA expressing the nucleocapsid protein of the JHM strain of mouse hepatitis virus into C57BL/6 mice", Journal of Veteterinary Medical Science, 58 : 731-735 (1996)*
  • T. Morimura, K. Ohashi, Y. Kon, M. Hattori, C. Sugimoto and M. Onuma, : "Apoptosis and CD8-down-regulation in the thymus in chickens infected with Marek's disease virus", Archivs of Virology, 141 : 2243-2249 (1996)*
    1996 [Not refereed][Not invited]
  • H. I. Ismail, Y. Hashimoto, Y. Kon, A. Konno, H. Yamazoe and T. Iwanaga : "Immunoglobulin-containing cells and T lymphocyte subpopulations in the mouse mammary gland. A morphometric and immunohistochemical study", Biomedical Research, 17 : 105-113 (1996)*
    1996 [Not refereed][Not invited]
  • M. Nagata, K. Tanimoto, A. Fukamizu, Y. Kon, F. Sugiyama, K. Yagami, K. Murakami and T. Watanabe : "Nephrogenesis and renovascular development in angiotensinogen-deficient mice", Laboratory Investigation, 75 : 745-753 (1996)*
    1996 [Not refereed][Not invited]
  • T. Yamashita, H. Ohshima, T. Asanuma, N. Inukai, I. Miyoshi, N. Kasai, Y. Kon, T. Watanabe, F. Sato and M. Kuwabara : "The effects of α-phenyl-tert-butylnitrone (PBN) on copper-induced rat fulminant hepatitis with jaundice", Free Radical Biology and Me・・・
    1996 [Not refereed][Not invited]
     
    T. Yamashita, H. Ohshima, T. Asanuma, N. Inukai, I. Miyoshi, N. Kasai, Y. Kon, T. Watanabe, F. Sato and M. Kuwabara : "The effects of α-phenyl-tert-butylnitrone (PBN) on copper-induced rat fulminant hepatitis with jaundice", Free Radical Biology and Medicine, 21 : 755-761 (1996)*
  • MORPHOLOGICAL EVIDENCE OF EXOCRINE FUNCTION IN COAGULATING GLAND RENIN OF MOUSE STRAIN C57BL/6
    Y KON, D ENDOH, K MURAKAMI, T YAMASHITA, T WATANABE, Y HASHIMOTO
    ANATOMICAL RECORD 243 (2) 200 - 207 0003-276X 1995/10 [Not refereed][Not invited]
     
    Background: Renin is classically secreted from juxtaglomerular cells of the kidney by endocrine or paracrine mechanisms. In a previous report, intense renin immunoreactivity was observed in the coagulating gland (CG), a new source for renin in mice. In the present study, immunoelectron microscopical analysis for renin was carried out to clarify the secretory site of CGs, Methods: Five adult male C57BL/6 mice were used in this study, The CGs were fixed with an ice-cold 2% glutaraldehyde and 2% paraformaldehyde mixture and embedded in Lowicryl K4M. Ultrathin sections were treated with antimouse renin antiserum and colloidal gold (15 nm)-labeled protein A complex. Results: In immunoelectron microscopical observation, renin was first detected at the Golgi vacuoles just budding from the lamellae, although it was not demonstrated in all Golgi vacuoles. In the production series of exocrine granules, renin immunoreactivity was observed in some granules that were distributed in the supranuclear region. Both renin-positive and -negative exocrine granules were secreted from the apical cell membrane by exocytosis. The lysosomal granules also showed stronger renin immunoreactivity and contained homogeneous or heterogeneous materials. In the supranuclear region, it was observed that exocrine granules were fused with irregular lysosomal granules. At the apical region, such lysosomal granules were closely associated with cell membrane. At the basolateral region, immunoreactivity for renin was localized in electron dense granules. Conclusions: These results suggest that part of the renin in the CGs is released by exocrine secretion into the genital tract. (C) 1995 Wiley-Liss, Inc.
  • DISTRIBUTION OF EPITHELIOID CELLS IN THE WALL OF THE CHICKEN AORTA AND THEIR FUNCTIONAL-ROLE AS CHEMORECEPTORS
    M MIYOSHI, Y HASHIMOTO, Y KON, M SUGIMURA
    ANATOMICAL RECORD 242 (3) 302 - 309 0003-276X 1995/07 [Not refereed][Not invited]
     
    Background: The ultrastructural characteristics of epithelioid cells in the wall of the chicken aorta have been studied by several investigators. Their characteristics were homologous to those of carotid body type I cells and are considered to be one of the peripheral chemoreceptors. However, there are few descriptions about their location, distribution, and how they react to chemical signals, nor have there been many reports about the localization of bioactive substances in the epithelioid cells. Therefore we designed this investigation to address these problems. Methods: Wholemount immunohistochemistry using antiserotonin antiserum, scanning (SEM), and transmission (TEM) electron microscopy were used to observe the epithelioid cells and the lumen of the chicken aorta. The localizations of bioactive substances in the epithelioid cells were immunohistochemically investigated using 11 antisera. Results: Epithelioid cells were dispersed in the wall of the aorta, forming a band similar to 1 mm in width, located 10 mm proximal to the confluence of the right and left Ligamenta arteriosa. Serotonin, chromogranin, and neuron specific enolase immunoreactivities were detected in the epithelioid cells. SEM observations clearly demonstrated intraendothelial fenestrations, 1-3 mu m in diameter, on the endothelial surface of the region of the band of epithelioid cells. TEM observations revealed that these fenestrations corresponded to endothelial gaps, directly beneath which epithelioid cells were sometimes located. Conclusions: The epithelioid cells are in direct access to the aortic lumen through endothelial fenestrations. Thus they may be able to perceive chemical signals from arterial blood directly. (C) 1995 Wiley-Liss, Inc.
  • EXPRESSION OF RENIN IN COAGULATING GLANDS IS REGULATED BY TESTOSTERONE
    Y KON, D ENDOH, K MURAKAMI, T YAMASHITA, T WATANABE, Y HASHIMOTO, M SUGIMURA
    ANATOMICAL RECORD 241 (4) 451 - 460 0003-276X 1995/04 [Not refereed][Not invited]
     
    Background: The presence of extrarenal or local renin-angiotensin system (RAS) has been noted in several tissues, although its functions have not yet been clarified. Renin from the coagulating gland (CG) is the most recently discovered local RAS and is a significant subject for investigation because large amounts of both mRNA and proteins are detected in this organ. Recently, it has been reported that testosterone influences renin synthesis in several extrarenal tissues, although it has no effect on intrarenal renin. Therefore, it is possible that CG renin is also regulated by testosterone. Methods: Forty-four male C57BL/6 mice, aged 3 wk to 6 mo, were used in studies on the ontogeny and androgen regulation of the RAS in the CG. The tissues were fixed with Bouin's solution and paraffin sections were stained with immunohistochemical methods using antirenin antiserum, In each inmunostained section, the relative number of renin-containing cells in terminal portions of the CG were counted. Results: Immunoreactivity for renin was first detected at 6 wk after birth. After that time, the number of renin-containing cells gradually increased throughout the experiment, In adults, several patterns of renin immunoreactivity were demonstrated in almost all epithelial cells of CGs, specifically; (1) basolateral granular reaction, (2) diffuse immunoreactivity throughout the cytoplasm, and (3) restricted nuclear reaction. Excretory products of some terminal lumina were also found to be positive for renin, At 10 days after castration, renin-containing cells in ductal termini were decreased and remained at low levels until at 4 wk after castration. After testosterone injection, numerical values of renin-containing cells were high at 1 wk and then decreased at 2-3 wk. Conclusion: It is suggested that CG renin of the mouse is expressed together with sexual maturation during development and that it depends on the testis, possibly the male sex hormone. (C)1995 Wiley-Liss, Inc.
  • Expression of the endogeneous Marek's disease virus ICP4 homolog (MDV ICP4) gene is enhanced in latently infected cells by transient transfection with the recombinant MDV ICP4 gene.
    Jpn. J. Vet. Res., 43 (3-4) 109 - 124 1995 [Not refereed][Not invited]
  • Expression of gd T cell receptor on caprine globule leukocytes.
    Vet. Immunol. Immunopathol., 48 105 - 112 1995 [Not refereed][Not invited]
  • 加来 義浩, 昆 泰寛, 高木 信夫, 山下 匡, 林 正信, 渡辺 智正
    J. Vet. Med. Sci., 57 (5) 973 - 975 0916-7250 1995 [Not refereed][Not invited]
  • CORTICAL EXPRESSION OF THE HUMAN ANGIOTENSINOGEN GENE IN THE KIDNEY OF TRANSGENIC MICE
    A FUKAMIZU, M WATANABE, Y INOUE, Y KON, S SHIMADA, N SHIOTA, F SUGIYAMA, K MURAKAMI
    KIDNEY INTERNATIONAL 46 (6) 1533 - 1535 0085-2538 1994/12 [Not refereed][Not invited]
     
    Cortical expression of the human angiotensinogen gene in the kidney of transgenic mice. We have previously generated ''Tsukuba hypertensive mice'' with elevated blood pressure by cross-mating separate lines of transgenic animals carrying either 15 kb of the human renin gene including its native 3-kb promoter or 14 kb of the human angiotensinogen gene along with its 1.3-kb promoter, the former of which is expressed predominantly in the kidney and the latter of which is also expressed in the kidney to levels comparable to those found in the liver. To investigate whether the integrated human angiotensinogen gene is prominently expressed in the kidney of transgenic mice, we have analyzed a production region of the transgene mRNA by in situ hybridization technique. This analysis clearly demonstrated that human angiotensinogen mRNA is localized specifically to the cortex region of transgenic mouse kidney. The present finding indicates a possible involvement of the renal renin-angiotensin system in the pathogenesis of high blood pressure in transgenic mice.
  • ANATOMICAL AND HISTOLOGICAL REEXAMINATION OF APPENDIXES COLLI IN THE GOAT
    T IMAGAWA, Y KON, H KITAGAWA, Y HASHIMOTO, M UEHARA, M SUGIMURA
    ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER 176 (2) 175 - 179 0940-9602 1994/04 [Not refereed][Not invited]
     
    Appendices colli (App. colli) were investigated by anatomical and histological methods in the goat. App. colli were composed of elastic cartilage located at central and the skin covering the cartilage, which included arterioles along the cartilage and nerve bundles. Three types of muscles connected to App. colli; superficial muscle bundles, a branch of the omohyoideus muscle, and a muscle arising from the pharyngeal raphe (appendico-pharyngeal muscle). The latter two muscles were connected to the root of the App. colli where the muscle fibers transformed into the perichondrium of the elastic cartilage. The appendico-pharyngeal muscle was innervated by branches from the glossopharyngeal nerve which were composed of myelinated nerve fibers. The subcutaneous area of the App. colli was supplied by cutaneous rami of the vagus and the second cervical nerves. The innervation and the musculature confirmed that the cartilage of the App. colli were derived from third and fourth branchial arches.
  • 今野 明弘, 橋本 善春, 昆 泰寛, 杉村 誠
    J. Vet. Med. Sci., 56 (6) 1101 - 1105 0916-7250 1994 [Not refereed][Not invited]
  • MAKI K, MIYOSHI I, KON Y, YAMASHITA T, SASAKI N, AOYAMA S, TAKAHASHI E, HAYASHIZAKI Y, KASAI N
    Mol. Cell. Endocrinol., . 105 (2) 147 - 154 0303-7207 1994 [Not refereed][Not invited]
  • Immunohistochemical studies of renin-containing cells in the developing sheep kidney.
    Anat. Rec., 239, 191-197. 239 191 - 197 1994 [Not refereed][Not invited]
  • ADRENAL RENIN IS LOCALIZED IN LYSOSOMAL GRANULES
    Y KON, Y HASHIMOTO, M SUGIMURA, K MURAKAMI
    ANATOMIA HISTOLOGIA EMBRYOLOGIA-JOURNAL OF VETERINARY MEDICINE SERIES C-ZENTRALBLATT FUR VETERINARMEDIZIN REIHE C 22 (4) 324 - 327 0340-2096 1993/12 [Not refereed][Not invited]
     
    Both renin an cathepsin B were co-localized in identical granules of adreno-cortical cells. At day 16 of gestation, many renin-containing granules were observed and gold particles showed homogeneous intragranular distribution; whereas, those for cathepsin B was distributed heterogeneously. At day 18 of gestation, renin immunoreactivity was decreased or undetectable, whereas cathepsin B was still demonstrated at the same level as on day 16 of gestation.
  • Morphological study on the vasculature of intestine in carp (Cyprinus carpio).
    J. Rakuno Gakuen Univ., 18 21 - 30 1993 [Not refereed][Not invited]
  • 昆 泰寛, 遠藤 大二, 深水 昭吉, 村上 和雄, 橋本 善春, 杉村 誠
    J. Vet. Med. Sci., 55 (3) 461 - 463 0916-7250 1993 [Not refereed][Not invited]
  • 小倉 知子, 昆 泰寛, 小沼 操, 近藤 高志, 橋本 善春, 杉村 誠
    J. Vet. Med. Sci., 55 (1) 59 - 66 0916-7250 1993 [Not refereed][Not invited]
  • HAYASHI M, ENDOH D, KON Y, YAMASHITA T, SATO F, KASAI N, NAMIOKA S
    J. Vet. Med. Sci., 55 (1) 13 - 18 0916-7250 1993 [Not refereed][Not invited]
  • COMPARATIVE-STUDY OF RENIN EXPRESSION IN THE COAGULATING GLANDS OF C57BL/6 AND BALB/C MICE
    Y KON, D ENDOH, A FUKAMIZU, K MURAKAMI, Y HASHIMOTO, M SUGIMURA
    JOURNAL OF ANATOMY 181 335 - 343 0021-8782 1992/10 [Not refereed][Not invited]
     
    The comparative localisation of renin in the genital organs, especially in the coagulating glands of male mice of the strains C57BL/6 and Balb/c, was investigated using immunocytochemical, immunoelectron microscopical and Northern blot techniques. Dot-like reactions for renin, of varying diameters, were detected immunocytochemically in the epithelial cells of coagulating glands of C57BL/6 mice, but not in those of Balb/c mice. In both strains, many electron dense granules differing in content and morphology were observed in the epithelial cells of the coagulating glands. Crystalline materials were sometimes contained in these granules. Colloidal gold particles indicating the presence of renin were detected in the electron dense granules of C57BL/6 mice, in which they showed a heterogeneous distribution and were especially located on the crystalline structure. No positive reaction was detected in these crystalline structures in Balb/c mice. Renin mRNA was detected in the coagulating glands of both C57BL/6 and Balb/c mice by Northern blot analysis. However, the expression in C57BL/6 coagulating glands was stronger than that in Balb/c. These findings suggest that renin is synthesised and released in the coagulating glands.
  • AN IMMUNOELECTRONMICROSCOPIC OBSERVATION OF MOUSE JUXTAGLOMERULAR CELLS IN THE CASE OF EXPERIMENTAL HYDRONEPHROSIS
    Y KON, Y HASHIMOTO, K MURAKAMI, M SUGIMURA
    ACTA ANATOMICA 144 (4) 354 - 362 0001-5180 1992/08 [Not refereed][Not invited]
     
    Changes in juxtaglomerular (JG; renin-containing) cells in experimental hydronephrosis 1 month after ureteral ligation were investigated with immunoelectron-microscopical techniques. Two types of granules. electron dense (D) and lucent (L), were observed. D type granules were labeled more intensely with gold particles than those of L type. Granules intermediate between D and L types and exocytosis of D types were observed. In the cells containing D types exclusively, gold particles were restricted to the granules, whereas in the cells containing both D and L type granules, the particles were scattered throughout the cytoplasmic cytosol. The authors discuss the mechanisms of renin release in JG cells.
  • MORPHOLOGICAL AND NORTHERN BLOT ANALYSIS OF JUXTAGLOMERULAR CELLS IN EXPERIMENTAL HYDRONEPHROTIC MICE
    Y KON, S TAKAHASHI, A FUKAMIZU, K MURAKAMI, Y HASHIMOTO, M SUGIMURA
    ANATOMICAL RECORD 232 (3) 393 - 400 0003-276X 1992/03 [Not refereed][Not invited]
     
    The purpose of this study is to demonstrate the developmental changes of the experimental hydronephrotic kidney using immunohistochemical, histoplanimetrical, and Northern blot techniques. At 1 month after ligation of the ureter, a large number of renin-positive cells were detected immunohistochemically even at a dilution of 1:10,000 in this hydronephrotic kidney; however, there were few renin-positive cells in the non-ligated side. At 6 months after ligation, no difference in reactivity for renin between ligated and non-ligated kidneys was demonstrated. In the morphometrical analysis of the renin-positive region, the numerical value of the ligated side was already increased at 2 weeks, reached the highest value at 1 month, and then decreased gradually to almost the same value as the control kidney by the end of the experiment. On the other hand, the value of the non-ligated side decreased immediately after the unilateral ligation, increased later, and finally reached almost the same value as the control kidney. In the Northern blot analysis, the activity of renin mRNA in the ligated side at 1 month after ligation was markedly higher than that in the non-ligated side. However, the difference between the ligated and the non-ligated sides was not demonstrated at 6 months and the value came to be almost the same as in the non-operated kidney.
  • KATO A, HASHIMOTO Y, KON Y, SUGIMURA M
    J. Vet. Med. Sci., 54 (5) 999 - 1006 0916-7250 1992 [Not refereed][Not invited]
  • Angioarchitecture of systemic and visceral circulation in carp (Cyprinus carpio).
    Zool. Jb. Anat., 122 43 - 53 1992 [Not refereed][Not invited]
  • 昆 泰寛, 橋本 善春, 村上 和雄, 杉村 誠
    J. Vet. Med. Sci., 54 (3) 589 - 590 0916-7250 1992 [Not refereed][Not invited]
  • HAYASHI M, ENDOH D, KON Y, YAMASHITA T, HASHIMOTO N, SATO F, KASAI N, NAMIOKA S
    J. Vet. Med. Sci., 54 (2) 269 - 273 0916-7250 1992 [Not refereed][Not invited]
  • HUMAN RENIN IN TRANSGENIC MOUSE KIDNEY IS LOCALIZED TO JUXTAGLOMERULAR CELLS
    A FUKAMIZU, T HATAE, Y KON, M SUGIMURA, T HASEGAWA, M YOKOYAMA, T NOMURA, M KATSUKI, K MURAKAMI
    BIOCHEMICAL JOURNAL 278 601 - 603 0264-6021 1991/09 [Not refereed][Not invited]
     
    To examine whether expression of human renin in the transgenic mouse kidney is regulated in a cell-specific manner, we have characterized monoclonal antibodies against human renin and determined the renin-production site by immunohistochemistry. By using a monoclonal antibody specific for human renin, A6-11-6, we demonstrated that human renin in the transgenic mouse kidney is localized to the juxtaglomerular cells of afferent arterioles.
  • CELL TYPE-SPECIFIC EXPRESSION OF THE HUMAN RENIN GENE
    A FUKAMIZU, S UEHARA, K SUGIMURA, Y KON, M SUGIMURA, T HASEGAWA, M YOKOYAMA, T NOMURA, M KATSUKI, K MURAKAMI
    JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS 5 (3) 112 - 116 0393-974X 1991/07 [Not refereed][Not invited]
     
    We have previously produced transgenic mice carrying the human renin gene, whose expression is regulated in a tissue-specific manner. In the present study, we further characterized expression of the transgene. Northern blot analysis showed that the human renin gene is expressed in the kidney but not in the liver of two lines of transgenic mice with 10 and 50 copies of the transgene, suggesting that the integrated copy number of the human renin gene does not influence the dominant-renal expression pattern. Immunohistochemical study using a monoclonal antibody specific for human renin demonstrated that expression of human renin in the transgenic mouse kidney is confined to the epitheloid juxtaglomerular cells. Transfection experiments indicated that the chloramphenicol acetyltransferase fusion gene containing the 3-kb upstream sequences of the renin gene is activated only in human epitheloid embryonic 293 cells derived from kidney but not in human HepG2 cells from liver. These findings suggest that transfer of the cloned renin gene into mice and in vitro cultured cell lines can give rise to cell type-specific expression.
  • An immunohistochemical study of the gastro-entero-pancreatic endocrine cells in the alimentary tract of the Korean tree squirrel, Sciurus vulgaris corea.
    Jpn. J. Vet. Res., 39 117 - 131 1991 [Not refereed][Not invited]
  • Localization of dopamine in the human ovary.
    Obstet. Gynecol. Therapy, 62 990  1991 [Not refereed][Not invited]
  • Immunoglobulin containing cells in the head kidney of carp (Cyprinus carpio L.) after bovine serum albumin injection.
    Fish Shellfish Immunol., 1 173 - 185 1991 [Not refereed][Not invited]
  • Intracellular production of adrenal renin in the fetal mouse. An immunoelectron microscopical study.
    J. Anat., 176, 23-33. 176 23 - 33 1991 [Not refereed][Not invited]
  • LECTIN HISTOCHEMISTRY AS SPECIAL MARKERS FOR RODLET CELLS IN CARP, CYPRINUS-CARPIO L
    T IMAGAWA, Y HASHIMOTO, Y KON, M SUGIMURA
    JOURNAL OF FISH DISEASES 13 (6) 537 - 540 0140-7775 1990/11 [Not refereed][Not invited]
  • VASCULARIZATION AND RELATED DISTRIBUTION OF LEUKOCYTES IN CARP, CYPRINUS-CARPIO L, HEAD KIDNEY
    T IMAGAWA, Y HASHIMOTO, Y KON, M SUGIMURA
    JOURNAL OF FISH BIOLOGY 37 (3) 357 - 366 0022-1112 1990/09 [Not refereed][Not invited]
  • RENIN IMMUNOHISTOCHEMISTRY IN THE ADRENAL-GLAND OF THE MOUSE FETUS AND NEONATE
    Y KON, Y HASHIMOTO, H KITAGAWA, M SUGIMURA, K MURAKAMI
    ANATOMICAL RECORD 227 (1) 124 - 131 0003-276X 1990/05 [Not refereed][Not invited]
  • 今川 智敬, 橋本 善春, 首藤 文栄, 昆 泰寛, 杉村 誠
    Jpn. J. Vet. Sci., 52 (6) 1329 - 1332 0021-5295 1990 [Not refereed][Not invited]
  • 杉村 誠, 白銀 大二, 阿閉 泰郎, 鈴木 義孝, 大島 一修, 昆 泰寛, 橋本 善春
    Jpn. J. Vet. Sci., 52 (5) 1015 - 1021 0021-5295 1990 [Not refereed][Not invited]
  • 君島 哲夫, 橋本 善春, 北川 浩, 昆 奏寛, 杉村 誠
    Jpn. J. Vet. Sci., 52 (2) 299 - 305 0021-5295 1990 [Not refereed][Not invited]
  • HISTOLOGICAL STUDY ON SEMINAL PLASMA ABSORPTION AND SPERMIOPHAGY IN THE EPIDIDYMAL REGION OF DOMESTIC-FOWL
    M NAKAI, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO
    POULTRY SCIENCE 68 (4) 582 - 589 0032-5791 1989/04 [Not refereed][Not invited]
  • AN IMMUNOHISTOCHEMICAL STUDY ON THE EMBRYONIC-DEVELOPMENT OF RENIN-CONTAINING CELLS IN THE MOUSE AND PIG
    Y KON, Y HASHIMOTO, H KITAGAWA, N KUDO
    ANATOMIA HISTOLOGIA EMBRYOLOGIA-JOURNAL OF VETERINARY MEDICINE SERIES C-ZENTRALBLATT FUR VETERINARMEDIZIN REIHE C 18 (1) 14 - 26 0340-2096 1989/03 [Not refereed][Not invited]
  • 今川 智敬, 橋本 善春, 北川 浩, 昆 泰寛, 工藤 規雄, 杉村 誠
    Jpn. J. Vet. Sci., 51 (6) 1163 - 1172 0021-5295 1989 [Not refereed][Not invited]
  • 中井 雅晶, 橋本 善春, 北川 浩, 昆 泰寛, 杉村 誠
    Jpn. J. Vet. Sci., 51 (3) 521 - 529 0021-5295 1989 [Not refereed][Not invited]
  • Histological and immunohistochemical studies on the localization of immunoglobulins in porcine placenta.
    Jpn. J. Vet. Res., 36 205 - 221 1988 [Not refereed][Not invited]
  • Jpn. J. Vet. Res., 36 83 - 117 1988 [Not refereed][Not invited]
  • Jpn. J. Vet. Res., 36 (1) 15 - 30 1988 [Not refereed][Not invited]
  • A scanning electron microscopic study on the architecture of the lymph vessels and the intranodal lymph pathways of lymph nodes in pigs.
    Jpn. J. Vet. Res., 36 (1) 1 - 14 1988 [Not refereed][Not invited]
  • 北川 浩, 橋本 善春, 昆 泰寛, 工藤 規雄
    Jpn. J. Vet. Sci., 50 (3) 638 - 647 0021-5295 1988 [Not refereed][Not invited]
  • 伊東 久男, 橋本 善春, 北川 浩, 昆 泰寛, 工藤 規雄
    Jpn. J. Vet. Sci., 50 (2) 395 - 404 0021-5295 1988 [Not refereed][Not invited]
  • 中井 雅晶, 橋本 善春, 北川 浩, 昆 泰寛, 工藤 規雄
    Jpn. J. Vet. Sci., 50 (2) 371 - 381 0021-5295 1988 [Not refereed][Not invited]
  • 昆 泰寛, 橋本 善春, 北川 浩, 工藤 規雄
    Jpn. J. Vet. Sci., 50 (2) 325 - 332 0021-5295 1988 [Not refereed][Not invited]
  • ARAI N, HASHIMOTO Y, KITAGAWA H, KON Y, KUDO N
    Jpn. J. Vet. Sci., 50, 183-192. 50 (1) 183 - 192 0021-5295 1988 [Not refereed][Not invited]
  • 伊東 久男, 橋本 善春, 北川 浩, 昆 泰寛, 工藤 規雄
    Jpn. J. Vet. Sci. 50 (1) 99 - 110 0021-5295 1988 [Not refereed][Not invited]
  • 伊東 久男, 橋本 善春, 北川 浩, 昆 泰寛, 工藤 規雄
    Jpn. J. Vet. Sci., 50 (1) 99 - 110 0021-5295 1988 [Not refereed][Not invited]
  • 星 信彦, 橋本 善春, 北川 浩, 昆 泰寛, 工藤 規雄
    Jpn. J. Vet. Sci., 50 (1) 83 - 92 0021-5295 1988 [Not refereed][Not invited]
  • 昆 泰寛, 橋本 善春, 北川 浩, 工藤 規雄
    Jpn. J. Vet. Sci., 49 (2) 323 - 331 0021-5295 1987 [Not refereed][Not invited]
  • Jpn. J. Vet. Sci., 48,/,1097-1107 1986 [Not refereed][Not invited]
  • Jpn. J. Vet. Sci., 48(5), 925-931. 925  1986 [Not refereed][Not invited]
  • 昆 泰寛, 橋本 善春, 北川 浩, 工藤 規雄
    Jpn. J. Vet. Sci. 46 (2) 189 - 196 0021-5295 1984 [Not refereed][Not invited]

Books etc

  • 獣医組織学 第七版
    日本獣医解剖学会 (Joint editor第1章 細胞学)
    学窓社 2017/03
  • 猫の解剖 カラーリングアトラス
    九郎丸正道, 監訳 (Joint editor図版62、63)
    学窓社 2014/09
  • Essentials of Domestic Animal Embryology
    山本, 谷口, 監訳 (OthersChapter 4 Gametogenesis)
    緑書房 2014/04
  • Veterinary Histology 6th edition
    日本獣医解剖学会 (Joint editorChapter 1 CYTOLOGY)
    学窓社 2014/03
  • Veterinary Histology 5th edition
    日本獣医解剖学会 (Joint editorChapter 1 CYTOLOGY)
    学窓社 2010/03
  • カラーアトラス獣医解剖学 増補改訂版
    カラーアトラス獣医解剖学編集委員会, 監訳 (Joint editor第7章 消化器系)
    緑書房 2010/03
  • Veterinary Histology 5th eition
    2010
  • Veterinary Embryology
    谷口, 木曽, 佐藤, 監修 (OthersChapter 22 Integumentary system)
    学窓社 2008/09
  • Veterinary Anatomy of Domestic Animals -Textbook and Colour Atlas-
    カラーアトラス獣医解剖学編集委員会, 監訳 (OthersChapter 7 Digestive system)
    チクサン出版社 2008/03
  • Veterinary Histology 4th edition
    日本獣医解剖学会 (Joint editorChapter 1 CYTOLOGY)
    学窓社 2008/03
  • Veterinary Histology 3rd edition
    日本獣医解剖学会 (Joint editorChapter 1 CYTOLOGY)
    学窓社 2005/03
  • 一般解剖学 VI-IX. In: 牧田登之、橋本善春 監訳. 犬の解剖アトラス、
    学窓社、東京、 1995

MISC

  • 獣医組織学 第七版
    昆 泰寛  学窓社  2017/03  [Not refereed][Not invited]
  • カラーアトラス動物発生学<山本雅子、谷口和美監訳>
    昆 泰寛  緑書房  2014/04  [Not refereed][Not invited]
  • 獣医組織学 第六版
    昆 泰寛  学窓社  2014/03  [Not refereed][Not invited]
  • 獣医組織学 第五版
    昆 泰寛  学窓社  2011/03  [Not refereed][Not invited]
  • 獣医発生学<谷口和之、木曽康郎、佐藤英明監訳>
    昆 泰寛  学窓社  2008/09  [Not refereed][Not invited]
  • カラーアトラス獣医解剖学(上下巻)<カラーアトラス獣医解剖学編集委員会監訳>>
    昆 泰寛  チクサン出版社  2008/03  [Not refereed][Not invited]
  • 獣医組織学 第四版
    昆 泰寛  学窓社  2007/03  [Not refereed][Not invited]
  • 動物を犠牲にしない獣医学教育の試みーEU圏の獣医解剖学と獣医外科学教育の現状についてー
    獣医臨床  24-  (12)  1  -8  2006  [Not refereed][Not invited]
  • 牛の解剖アトラス<日本獣医解剖学会監訳>
    昆 泰寛  緑書房  2005/03  [Not refereed][Not invited]
  • 獣医組織学 第三版
    2005  [Not refereed][Not invited]
  • 犬の解剖カラーリングアトラス<日本獣医解剖学会監訳>
    昆 泰寛  学窓社  2003/10  [Not refereed][Not invited]
  • 『犬の解剖アトラス(第2版)』
    学窓社  2002  [Not refereed][Not invited]

Awards & Honors

  • 1999/04 日本獣医学会 日本獣医学会賞
     レニン産生細胞の発生機序と新機能に関する研究 
    受賞者: 昆 泰寛

Research Grants & Projects

  • コットンラット:複数疾患を具有する実験用齧歯目のヒト併存症モデルへの応用
    学術振興会:科学研究費
    Date (from‐to) : 2018/04 -2021/03 
    Author : 中村鉄平
  • 体液顕微解剖の実践:原尿中エクソソーム由来マイクロRNAに腎障害マーカーを求めて
    学術振興会:科学研究費
    Date (from‐to) : 2018/04 -2020/03 
    Author : 市居 修
  • Mechanism of intestinal flexure
    学術振興会:科学研究費
    Date (from‐to) : 2013/04 -2015/03 
    Author : KON Yasuhiro
  • Molecular anatomy concerning autoimmune diseases and sterilities -relationship between onset of diseases and spermatogenetic checkpoint-
    学術振興会:科学研究費
    Date (from‐to) : 2012/04 -2015/03 
    Author : KON Yasuhiro
  • 精巣内卵細胞の解析
    科学研究費補助金
    Date (from‐to) : 2007
  • Analysis for intratesticular oocytes
    Grant-in-Aid for Scientific Research
    Date (from‐to) : 2007
  • ネフロン形成の分子基盤
    Date (from‐to) : 2000
  • 精巣内アポトーシスの解析
    Date (from‐to) : 2000
  • Analysis of apoptosis in testis
    Date (from‐to) : 2000

Educational Activities

Teaching Experience

  • 獣医科学・感染症学基礎科目 研究機器演習
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • Inter-Graduate School Classes(Educational Program):Museology
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
    キーワード : 学術標本・資料、博物館、学芸員、アドバンストコース
  • 獣医科学特別研究
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • Practice in Histology
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 顕微鏡、細胞、上皮組織、結合組織、支持組織、筋組織、神経組織、消化器系、呼吸器系、尿生殖器系、内分泌系、免疫系、神経系、感覚器、外皮、鳥類組織学、免疫組織学、超微形態学
  • 専門獣医科学特論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • Fish Diseases
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 魚病、魚類、水産、感染症
  • 獣医科学特論演習
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • Anatomy
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 骨学、筋学、脈管学、神経学、内臓学、肉眼解剖学、解剖学用語
  • 獣医科学基礎科目B 研究機器演習
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • Short Term Field Practice
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 主体的インターンシップ、臨床実習、動物病院、動物園、博物館、牧場
  • 先端獣医科学特論B 生命科学特論Ⅳ:発生生物工学
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • Long Term Field Practice
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 主体的インターンシップ、臨床実習、動物病院、動物園、博物館、牧場
  • 獣医科学特別研究
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • Freshman Seminar
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 動物、器官、臓器、組織、構造、細胞、発生
  • 獣医科学特論演習
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • Embryology
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 発生生物学、モデル動物、前発生、始原生殖細胞、卵割、着床、胎膜(卵黄嚢、栄養膜、羊膜、尿膜、絨毛膜、胎盤)、外胚葉、中胚葉、内胚葉、神経管、神経堤、心内膜筒、心ループ、心内膜隆起、大動脈弓、主静脈、卵黄嚢静脈、臍静脈、咽頭弓、前腸、中腸、後腸、中腎管、中腎傍管、尿管芽、生殖索、膜性骨化、軟骨性骨化
  • 獣医科学基礎科目 研究機器演習
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • Veterinary Laws and Regulations
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 法規、獣医学、獣医師、獣医療、獣医業、薬事、公衆衛生、食品衛生、動物衛生、環境衛生
  • 獣医科学基礎科目 生命科学特論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • Veterinary Ethics
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 生命倫理、獣医倫理、動物福祉、伴侶動物、産業動物、実験動物、展示動物、野生動物
  • 先端獣医科学科目 先端生命科学特論Ⅰ:発生生物学
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • Histology
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 細胞、上皮組織、結合組織、支持組織、筋組織、神経組織、消化器系、呼吸器系、尿生殖器系、内分泌系、免疫系、神経系、感覚器、外皮、鳥類組織学
  • 専門獣医科学特論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • Elementary Seminar in Veterinary Science at Sapporo
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 獣医学、大学、研究
  • 獣医学英語演習
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • Elementary Seminar in Biosciences
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 獣医学、自学自習、PBL学習、英語演習
  • 獣医学総合演習
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • Introduction to Veterinary Medicine
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 獣医学、獣医師、伴侶動物、産業動物、野生動物、公衆衛生、動物実験
  • 獣医学総合実習
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • Practice in Anatomy
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 骨学、筋学、脈管学、神経学、内臓学、肉眼解剖学、解剖学用語
  • 卒業論文
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 獣医臨床形態機能学演習
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 現地実習
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 生物科学基礎演習
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 研究・臨床セミナー
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • アドバンスト演習
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部

Campus Position History

  • 2013年4月1日 
    2014年3月31日 
    教育研究評議会評議員
  • 2014年4月1日 
    2016年3月31日 
    教育研究評議会評議員
  • 2016年4月1日 
    2017年3月31日 
    教育研究評議会評議員
  • 2017年4月1日 
    2019年3月31日 
    教育研究評議会評議員
  • 2017年4月1日 
    2019年3月31日 
    大学院獣医学院長
  • 2019年4月1日 
    2021年3月31日 
    教育研究評議会評議員
  • 2019年4月1日 
    2021年3月31日 
    大学院獣医学院長

Position History

  • 2013年4月1日 
    2014年3月31日 
    教育研究評議会評議員
  • 2014年4月1日 
    2016年3月31日 
    教育研究評議会評議員
  • 2016年4月1日 
    2017年3月31日 
    教育研究評議会評議員
  • 2017年4月1日 
    2019年3月31日 
    教育研究評議会評議員
  • 2017年4月1日 
    2019年3月31日 
    大学院獣医学院長
  • 2019年4月1日 
    2021年3月31日 
    教育研究評議会評議員
  • 2019年4月1日 
    2021年3月31日 
    大学院獣医学院長

Social Contribution

Social Contribution

Social Contribution

  • 佐藤新渡戸記念寮
    Role : Organizing member


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