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Morimatsu Masami

Faculty of Veterinary Medicine　Veterinary Medicine　Applied Veterinary SciencesProfessor
One Health Research CenterProfessor

Researcher basic information

■ Degree
  • PhD, Hokkaido University
■ URL
researchmap URLホームページURL■ Various IDs
Researcher number
  • 70241370
J-Global ID■ Research Keywords and Fields
Research Keyword
  • 獣医生化学
  • 分子遺伝学
  • 実験動物学
  • Veterinary Biochemistry
  • Molecular Genetics
  • Laboratory Animal Science
Research Field
  • Life Science, Experimental pathology
  • Life Science, Veterinary medical science
  • Life Science, Laboratory animal science
■ Educational Organization

Career

■ Career
Career
  • Apr. 2022 - Present
    Faculty of Veterinary Medicine Hokkaido University, Laboratory of Laboratory Animal Science and Medicine Department of Applied Veterinary Sciences, Professor
  • Nov. 2013 - Dec. 2022
    Faculty of Veterinary Medicine, Hokkaido University, Attending Veterinarian of Animal Facility
  • Nov. 2013 - Mar. 2022
    Faculty of Veterinary Medicine, Hokkaido University, Laboratory of Laboratory Animal Science and Medicine Department of Applied Veterinary Sciences, Associate Professor
  • Apr. 2012 - Oct. 2013
    Institute for Genetic Medicine, Hokkaido University, Laboratory of Animal Experiments, Director
  • Jul. 2008 - Oct. 2013
    Institute for Genetic Medicine, Hokkaido University, Disease Model Innovation, Associate Professor
  • Apr. 2007 - Oct. 2013
    Institute for Genetic Medicine, Hokkaido University, Laboratory of Animal Experiments, Associate Professor
  • Oct. 2005 - Mar. 2007
    Institute for Genetic Medicine, Hokkaido University, Laboratory of Animal Experiments, Associate Professor
  • 2004 - 2005
    Graduate School of Medicine, Hokkaido University, Laboratory of Histology and Cytology, Assistant Professor
  • 1997 - 2004
    Faculty of Agriculture, Iwate University, Laboratory of Physiology, Department of Veterinary Medicine, Associate Professor
  • 1996 - 1997
    University of Texas MD Anderson Cancer Center, Visiting Fellow
  • 1992 - 1997
    Graduate School of Veterinary Medicine, Hokkaido University, Laboratory of Biochemistry, Assistant Professor
  • 1995 - 1995
    University of São Paulo School of Medicine, Visiting Fellow
Educational Background
  • Mar. 1992, Hokkaido University, Graduate School of Veterinary Medicine, 形態機能学, Japan
  • 1992, Hokkaido University, Graduate School, Division of Veterinary Medicine
  • 1989, Hokkaido University, Faculty of Veterinary Medicine
  • Mar. 1987, Hokkaido University, School of Veterinary Medicine, Veterinary Medicine, Japan
Committee Memberships
  • 2024 - Present
    The Japanese Association of Laboratory Animal Facilities of National University Corporation, Vice President
  • Feb. 2023 - Present
    Editorial Board Member "Animals", Others
  • 2023 - Present
    Japanese Society for Laboratory Animal Medicine, Committee for Legal and Regulatory Affairs（Chair）
  • May 2022 - Present
    Japanese Association for Laboratory Animal Science (JALAS), Assessment and Verification Committee, Society
  • May 2022 - Present
    Japanese Association for Laboratory Animal Science (JALAS), Board of Directors, Society
  • Apr. 2022 - Present
    Japanese College of Laboratory Animal Medicine (JCLAM), Board of Directors, Society
  • 2022 - Present
    The Japanese Association of Laboratory Animal Facilities of National University Corporation, Assessment and Verification Committee
  • 2020 - Present
    Japanese Association for Laboratory Animal Science (JALAS), Committee for the Act on Welfare and Management of Animals and its related matters, Society
  • 2020 - Present
    Japanese Association for Laboratory Animal Science (JALAS), Committee for Training System of Laboratory Animal Manager, Society
  • Mar. 2019 - Present
    Editorial Board Member of "Biomedical Research", Others
  • 2018 - Present
    Japanese Association for Laboratory Animal Science (JALAS), Committee for laboratory animal welfare and ethics
  • 2016 - Present
    Japanese Association for Laboratory Animal Science (JALAS), Committee for the Training of Site Visitors in Verification and Validation Programs for Proper Conduct of Animal Experimentations, Society
  • 2014 - Present
    Japanese Association for Laboratory Animal Medicine (JALAM), Board of Directors, Society

Research activity information

■ Papers
  • Protoscolex Maturation in Echinococcus multilocularis Is Controlled by Host Genetic Factors Independent of Initial Development
    Moe Kogawa; Keisuke Sato; Teppei Nakamura; Naoki Hayashi; Hirokazu Kouguchi; Ryo Nakao; Masahito Hidaka; Hiroyuki Matsuyama; Nariaki Nonaka; Osamu Ichii; Takashi Agui; Masami Morimatsu
    Parasite Immunology, 48, 2, Wiley, 16 Feb. 2026
    Scientific journal, ABSTRACT

    Alveolar echinococcosis, caused by Echinococcus multilocularis , poses a serious public health concern. This parasite requires rodents as intermediate hosts for protoscolex maturation in the liver and subsequent transmission to definitive hosts. We aimed to identify the host genetic factors controlling protoscolex development and maturation in congenic mice carrying susceptible DBA/2 genomic segments on a resistant C57BL/6N background. We assessed the hepatic protoscoleces and immune‐related gene expression levels 16 weeks post‐oral infection. All congenic strains developed protoscoleces; however, the number and proportion of mature forms decreased as C57BL/6N‐derived genomic contribution on chromosome 1 increased. Differences in DBA/2‐derived segments revealed two loci, E. multilocularis protoscolex maturation 1 ( Empmat1 ) and 2 ( Empmat2 ), as regulators of protoscolex maturation, but not early development, where immune involvement was limited. T‐box transcription factor 21 expression was correlated with protoscolex maturation; however, it lay outside Empmat1 and Empmat2 and was unlikely to be the responsible gene. Therefore, protoscolex maturation is potentially regulated by multiple host genetic factors distinct from those involved in early development, with B6‐derived alleles exerting inhibitory effects, possibly via non‐immune host mechanisms. Elucidation of these genetic pathways can reveal novel targets to disrupt the life cycle and reduce the zoonotic transmission of E. multilocularis .
  • Efferocytosis-Driven M2 Macrophage Impairs Fibrotic Encapsulation and Promotes Echinococcus multilocularis Growth in Cotton Rats (Sigmodon hispidus).
    Maru Manabe; Teppei Nakamura; Keisuke Sato; Naoki Hayashi; Hirokazu Kouguchi; Ryo Nakao; Masahito Hidaka; Hiroyuki Matsuyama; Nariaki Nonaka; Masami Morimatsu
    Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada, 31, 5, 03 Sep. 2025, [International Magazine]
    English, Scientific journal, Alveolar echinococcosis, caused by Echinococcus multilocularis, exhibits significant species-dependent susceptibility. This study compared the early hepatic tissue responses to E. multilocularis in highly susceptible cotton rats (Sigmodon hispidus) and laboratory mice (DBA/2 and AKR/N). Following oral administration of E. multilocularis eggs, cotton rats developed a greater number of hepatic lesions within 2 weeks, whereas mice required 4 weeks to develop smaller lesions. Histopathology revealed accelerated multilocular cyst formation in cotton rats. Unlike mice, which formed dense collagenous layers isolating cysts, cotton rats lacked adventitial layers despite similar fibrotic thickness. Immunohistochemistry revealed abundant CD206+ macrophages at cyst peripheries in cotton rats, engaging in efferocytosis of apoptotic neutrophils with expression of TGF-β, galectin-3, and VEGF. Efferocytic macrophages expressed collagen-degrading enzymes (cathepsin K and MMP9) and the growth factor FGF2. These findings suggest that efferocytosis by neutrophils drives macrophages toward an anti-inflammatory M2 phenotype, leading to immune evasion, ineffective fibrotic encapsulation, and parasitic growth. Given the wide distribution of cotton rats in the Americas and the expanding range of E. multilocularis, their hypersusceptibility raises significant public health concerns as rodents could serve as an intermediate host. These insights may inform new strategies for host-parasite interactions and the control of alveolar echinococcosis.
  • Dual-route medetomidine-alfaxalone-butorphanol anesthesia: a refined protocol for balanced anesthesia in male rabbits.
    Risa Iwanaga; Munekatsu Ita; Kanako Sumi; Chizuko Kodama; Mohammad Ibrahim Qasimi; Jun Tamura; Ko Nakanishi; Kayoko Matsumura; Masami Morimatsu; Yasuhiro Yoshida; Teppei Nakamura
    Experimental animals, 15 Apr. 2025, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Injectable anesthesia is widely used in laboratory animals because of its ease of administration and minimal equipment requirements. However, it necessitates careful monitoring as well as thermal and oxygen support. This study evaluated the efficacy of medetomidine-alfaxalone-butorphanol (MAB) anesthesia in male rabbits using a dual-route administration protocol. The anesthetic doses were as follows: medetomidine, 0.2 mg/kg; alfaxalone, 2.0 mg/kg; and butorphanol, 2.0 mg/kg. MAB anesthesia, administered via intravenous and subcutaneous routes, induced rapid and smooth induction, achieving anesthetic scores comparable to those of medetomidine-midazolam-butorphanol (MMB) anesthesia. MAB anesthesia resulted in mild hypothermia during the procedure. Upon atipamezole administration, rabbits under MAB anesthesia exhibited faster recovery of the righting reflex and respiration rate than those under MMB. Importantly, no abnormal behaviors, such as jumping or agitation, were observed during induction or recovery, as reported with alfaxalone use in other species. Both protocols maintained spontaneous breathing, although transient hypoxemia was observed in all rabbits. The dual-route MAB protocol provided effective anesthesia while addressing the limitations of conventional MMB anesthesia in rabbits, suggesting its potential as a refined anesthetic method for this species. Unlike mice, which showed weaker anesthetic effects with MAB compared to MMB, MAB demonstrated superior anesthetic properties in rabbits. This study highlights the importance of species-specific anesthetic protocols and the potential benefits of MAB anesthesia in rabbits, particularly its smooth induction and recovery profile, without adverse behaviors often associated with alfaxalone in other species.
  • Narrowing the region of candidate genes that control the development of protoscoleces of Echinococcus multilocularis in the mouse liver.
    Keisuke Sato; Naritaka Hikosaka; Hirokazu Kouguchi; Takao Irie; Masami Morimatsu; Takashi Agui
    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 127, 105704, 105704, Jan. 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Alveolar echinococcosis is a zoonosis caused by the larval stage of Echinococcus multilocularis. In previous studies, QTL analysis using C57BL/6 N (B6) and DBA/2 (D2) which differ in susceptibility suggested the presence of genes on chromosome 1 that control protoscolex development. In this study, we constructed several congenic mice with different chromosome 1 regions substituted to confirm the presence of responsible genes and to narrow down the regions where the responsible genes exist. Five lines of third-generation congenic strain were constructed and infection experiments were conducted. The results showed that the development of protoscolex was seen in the two lines, resulting to narrow-down the responsible region between 69.4 cM and 70.67 cM. There were 18 genes having different SNPs and 10 genes having amino acid substitutions between B6 and D2 within this region. Infection experiments with third-generation of congenic mice succeeded in narrowing down the chromosomal region determining protoscolex development, resulting to reduce the number of candidate genes. The identification of the gene responsible for protoscolex development will contribute to the control of E. multilocularis infection.
  • Dual-route administration of balanced anesthesia using medetomidine, midazolam, and butorphanol provides both suitable anesthetic depth and reduced tissue injury in rabbits.
    Risa Iwanaga; Kanako Sumi; Chizuko Kodama; Munekatsu Ita; Mohammad Ibrahim Qasimi; Jun Tamura; Ko Nakanishi; Yasuhiro Yoshida; Masami Morimatsu; Kayoko Matsumura; Teppei Nakamura
    Experimental animals, 23 Nov. 2024, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Medetomidine, midazolam, and butorphanol (MMB) anesthesia is the preferred choice for rodents but requires excess volume of intramuscular injection in rabbits, which can lead to muscular damage. This study aimed to evaluate a dual-route MMB administration via the intravenous and subcutaneous routes in rabbits. MMB was administered to male Kbs:JW rabbits with an intravenous injection of 0.2 mL/kg followed by a subcutaneous injection of 0.8 mL/kg, totaling 0.2 mg/kg medetomidine, 2.0 mg/kg midazolam, and 2.0 mg/kg butorphanol. We compared the anesthetic effects of this dual-route method with those of intramuscular administration. The dual-route method resulted in a shorter induction time and similar anesthetic duration compared with those of the intramuscular route. While it induced a temporary decrease in body temperature within 30 min post-injection, other vital signs, such as respiration rate, heart rate, and O2 saturation, remained similar. Notably, unlike intramuscular administration, dual-route administration did not increase tissue injury marker levels. This dual-route MMB administration provided sufficient anesthetic depth during surgery, eliminating pain reflexes. Double-dose administration extended anesthetic duration but resulted in rare fatalities, indicating room for protocol improvement. In conclusion, the novel anesthetic method is preferable for injectable anesthesia in rabbits, providing rapid induction and sufficient anesthetic duration, while potentially minimizing muscle injury. This technique may be beneficial for both laboratory and companion animals and significantly enhance animal welfare in anesthesia by reducing the pain associated with injectable anesthesia.
  • Functional Analysis of Oligoadenylate Synthetase in the Emu (Dromaius novaehollandiae).
    Keisuke Sato; Teppei Nakamura; Masami Morimatsu; Takashi Agui
    Animals : an open access journal from MDPI, 14, 11, 27 May 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 2'-5'-oligoadenylate synthetase (OAS) is one of the proteins that act as a defense mechanism against foreign RNA in cells. OAS has two functions: an antiviral effect against a wide range of virus species via the OAS/RNase L pathway with synthesized oligoadenylates and inhibition of viral replication specific to viruses of the genus Flavivirus, which is independent of enzymatic activity. Several birds have been reported to possess only one type of OAS family member, OASL, which has both enzymatic activity and inhibitory effects on flaviviral replication. However, the ostrich has two types of OASs, OAS1 and OASL, which show different functions-enzymatic and anti-flaviviral activities, respectively. In this study, emu OASs were cloned to investigate their sequence and function and elucidate the role of OASs in emus. The cloning results showed that emus had OAS1 and OASL, suggesting that emu OASs were more closely related to ostrich than to other birds. Functional investigations showed that emu OAS1 and OASL had enzymatic and anti-flaviviral activities, respectively, similar to those of the ostrich. Emus and ostriches are evolutionarily different from most birds and may be more closely related to mammalian OAS diversity.
  • Mouse oligoadenylate synthetase 1b inhibits West Nile virus replication by acting through the stem-loop 2 in the 3′-untranslated region
    Keisuke Sato, Teppei Nakamura, Masami Morimatsu, Takashi Agui
    Japanese Journal of Veterinary Research, 72, 2, 65, 70, 2024, [Peer-reviewed]
    English, Scientific journal
  • A Highly Conserved Region in BRCA2 Suppresses the RAD51-Interaction Activity of BRC Repeats.
    Zida Zhu; Taisuke Kitano; Masami Morimatsu; Kazuhiko Ochiai; Toshina Ishiguro-Oonuma; Kosuke Oosumi; Xianghui Lin; Koichi Orino; Yasunaga Yoshikawa
    Veterinary sciences, 10, 2, 10 Feb. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Mammary tumors are the most prevalent type of tumors in female dogs. Breast cancer 2, early onset (BRCA2) malignant mutations are associated with tumorigenesis in humans and dogs. BRCA2 plays a pivotal role in homologous recombination repair by recruiting RAD51 recombinase to DNA damage sites to maintain genome stability. To recruit RAD51, BRCA2 must interact with RAD51 via BRC repeats, but the regulation of this interaction has been unclear. In this study, we focused on a highly conserved region (HCR) near BRC repeats. Using co-immunoprecipitation and mammalian two-hybrid assay, we found that HCR suppressed the RAD51-interaction activity of BRC repeats and that substitutions of HCR phosphorylation sites affected it. In canine tumor samples, we found ten mutations, including a novel HCR mutation (I1110M) from canine tumor samples. The effect of four HCR mutations, including I1110M, on the RAD51-interaction activity of BRC repeats was tested. One of the HCR mutations found in canine mammary tumors increased the interaction, but the two mutations found in human breast cancers decreased it. This study suggested that the HCR regulated the RAD51-interacting activity of BRC repeats through HCR phosphorylation and that mutations in HCR may be related to tumorigenesis in both dogs and humans.
  • Canine Mammary Tumor Cell Lines Derived from Metastatic Foci Show Increased RAD51 Expression but Diminished Radioresistance via p21 Inhibition.
    Kei Shimakawa; Kazuhiko Ochiai; Sachi Hirose; Eri Tanabe; Masaki Michishita; Motoharu Sakaue; Yasunaga Yoshikawa; Masami Morimatsu; Tsuyoshi Tajima; Masami Watanabe; Yoshikazu Tanaka
    Veterinary sciences, 9, 12, 17 Dec. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Due to the high incidence of mammary tumors in dogs, it is important to elucidate the pathogenesis of these tumors in veterinary medicine. Radiation therapy is often used to treat mammary tumors that target DNA lesions. RAD51 is a key molecule that repairs DNA damage via homologous recombination. We examined the relationship between RAD51 expression and radiosensitivity in mammary tumor cell lines. CHMp and CHMm from the same individual were selected based on the differences in RAD51 expression. The radiosensitivity of both cell lines was examined using MTT and scratch assays; CHMm, which has high RAD51 expression, showed higher sensitivity to radiation than CHMp. However, the nuclear focus of RAD51 during DNA repair was formed normally in CHMp, but not in most of CHMm. Since irradiation resulted in the suppression of cell cycle progression in CHMp, the expression of p21, a cell cycle regulatory factor, was detected in CHMp after 15 Gy irradiation but not in CHMm. These results indicate that functional expression is more important than the quantitative expression of RAD51 in canine mammary tumor cells in response to DNA damage.
  • In vitro anticancer effects of alpelisib against PIK3CA‑mutated canine hemangiosarcoma cell lines.
    Marika Maeda; Kazuhiko Ochiai; Masaki Michishita; Masami Morimatsu; Hiroki Sakai; Nayuta Kinoshita; Motoharu Sakaue; Eri Onozawa; Daigo Azakami; Masami Yamamoto; Katsumi Ishioka; Takuya Sadahira; Masami Watanabe; Yoshikazu Tanaka
    Oncology reports, 47, 4, Apr. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Hemangiosarcoma (HSA) is a malignant neoplasm that occurs in humans and canines with a poor prognosis owing to metastatic spread, despite effective treatment. The frequency of spontaneous HSA development is higher in canines than in humans. Therefore, canine HSA is a useful model of intractable human disease, which requires early detection and an effective therapeutic strategy. A high frequency of the p110α phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit alpha (PIK3CA) mutations is detected in a comprehensive genome‑wide analysis of canine cases of HSA. The present cloned the full‑length cDNA of canine PIK3CA and identified a mutation in codon 1047 from canine cases of HSA and cell lines that were established from these. The enforced expression of the 1047th histidine residue (H1047)R or L mutants of canine PIK3CA in HeLa cells enhanced epidermal growth factor receptor (EGFR) signaling via Akt phosphorylation. PIK3CA mutant canine HSA cell lines exhibited the hyperphosphorylation of Akt upon EGF stimulation as well. Alpelisib, a molecular targeted drug against PIK3CA activating mutations, exerted a significant antitumor effect in canine PIK3CA‑mutated HSA cell lines. By contrast, it had no significant effect on canine mammary gland tumor cell lines harboring PIK3CA mutations. On the whole, the findings of the present study suggest that alpelisib may be highly effective against PIK3CA mutations that occur frequently in canine HSA.
  • BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents
    Zida Zhu; Taisuke Kitano; Masami Morimatsu; Arisa Tanaka; Ryo Morioka; Xianghui Lin; Koichi Orino; Yasunaga Yoshikawa
    International Journal of Molecular Sciences, 23, 7, Apr. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Breast cancer type 2 susceptibility (BRCA2) protein is crucial for initiating DNA damage repair after chemotherapy with DNA interstrand crosslinking agents or X-ray irradiation, which induces DNA double-strand breaks. BRCA2 contains a C-terminal RAD51-binding domain (CTRBD) that interacts with RAD51 oligomer-containing nucleofilaments. In this study, we investigated CTRBD expression in cells exposed to X-ray irradiation and mitomycin C treatment. Surprisingly, BRCA2 CTRBD expression in HeLa cells increased their resistance to X-ray irradiation and mitomycin C. Under endogenous BRCA2 depletion using shRNA, the sensitivities of the BRCA2-depleted cells with and without the CTRBD did not significantly differ. Thus, the resistance to X-ray irradiation conferred by an exogenous CTRBD required endogenous BRCA2 expression. BRCA2 CTRBD-expressing cells demonstrated effective RAD51 foci formation and increased homologous recombination efficiency, but not nonhomologous end-joining efficiency. To the best of our knowledge, our study is the first to report the ability of the BRCA2 functional domain to confer resistance to X-ray irradiation and mitomycin C treatment by increased homologous recombination efficiency. Thus, this peptide may be useful for protecting cells against X-ray irradiation or chemotherapeutic agents.
  • The number of glutamines in the N-terminal of the canine androgen receptor affects signalling intensities.
    Kazuhiko Ochiai; Samak Sutijarit; Mitsuki Uemura; Masami Morimatsu; Masaki Michishita; Eri Onozawa; Marika Maeda; Takanori Sasaki; Masami Watanabe; Yoshikazu Tanaka; Toshinori Omi
    Veterinary and comparative oncology, 19, 2, 399, 403, Jun. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Most male dogs are castrated at young ages, making them easy to rear following androgen deprivation. Although the incidence of canine prostate cancer is low, several patients have resistance to androgen therapy and poor clinical prognosis. These outcomes are similar to those of end-stage human androgen-independent prostate cancer. The androgen receptor (AR) of canines has two polyglutamine (polyQ) sequences (Q × 10 and Q × 23) at its N-terminal. The length of polyQ may be a risk factor for the development of prostate cancer in dogs; however, there is no evidence to support this. Hence, we artificially created polyQ deletion mutants of canine AR and evaluated their effects on AR signalling. The deletions of Q × 10 and Q × 23 were associated with significant reductions in AR signalling intensities. The Q × 10 mutants, which increase or decrease Q sequentially, also altered AR signalling. Furthermore, the Q × 10 deletion mutant, compared with the Q × 10 control, altered the intensities of the binding of polyQ to the C-terminal of AR, which contains a ligand-binding domain; this was not observed with the Q × 9, 11, and 12 variants. The number of glutamines in the N-terminals of canine ARs may influence AR signalling intensities and contribute to the risk of prostate cancer in dogs.
  • Identification of the core motif of the BRCA2 C-terminal RAD51-binding domain by comparing canine and human BRCA2.
    Yasunaga Yoshikawa; Masami Morimatsu; Kazuhiko Ochiai; Toshina Ishiguro-Oonuma; Ryo Morioka; Kento Okuda; Koichi Orino
    The Journal of veterinary medical science, 83, 5, 759, 766, 09 May 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Mammary tumors are the most common tumors in women and non-spayed female dogs. One of the reasons for mammary tumors is mutations of the tumor suppressor gene, BRCA2. BRCA2 participates in homologous recombination repair by interacting with the RAD51 recombinase. BRCA2 has two RAD51-binding domains, consisting of BRC repeats and the C-terminal RAD51-binding domain, respectively. Although several studies have addressed the function of the C-terminal RAD51-binding domain of human BRCA2, the amino acid sequences required for the RAD51-interaction activity remain unclear. In this study, the C-terminal RAD51-binding domains of canine and human BRCA2 were compared; the canine domain displayed a weaker interaction with RAD51. This difference was attributed to the C-terminal portion of the domain via a comparison between canine and human domains. Furthermore, peptides shorter than those previously reported displayed RAD51-interacting activity, and a core motif of this domain consisting of 25 amino acids was identified. Since a mutation (S3323N) was reported in the core motif of this domain, the effect of this mutation was evaluated. The mutant exhibited similar RAD51-binding activity as that of the wild-type protein, suggesting that the mutation was functionally neutral. These data suggested that the C-terminal portion of the BRCA2 C-terminal RAD51-binding domain influenced its RAD51-interaction activity, and a minimum core motif of 25 amino acids was identified in this domain. These data may help clarify BRCA2 function, as well as the tumorigenic effects of BRCA2 mutation.
  • The response of adipose tissues to Mycoplasma pulmonis and Sendai virus infection in C57BL/6 and DBA/2 mice.
    Tussapon Boonyarattanasoonthorn; Keisuke Sato; Yuko Okamatsu-Ogura; Masami Morimatsu; Takashi Agui
    The Journal of veterinary medical science, 83, 3, 403, 411, 11 Mar. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Adipose tissues in mammals are categorized into white and brown adipose tissues in which cellular morphology, cell functions, and tissue distribution are different. White adipose tissue (WAT) plays a major role in energy reservation, while brown adipose tissue (BAT) mainly relates to the thermoregulation of the body. One interesting function of adipose tissue is the response to the infection, especially the pathogens that cause pneumonia. We have previously reported that DBA/2 (D2) mice are susceptible to pathogens causing pneumonia, Mycoplasma (M.) pulmonis and Sendai virus (SeV), whereas C57BL/6 (B6) mice are resistant to them. Furthermore, morphological alteration of mediastinal fat tissue (MFT) was seen after infection of M. pulmonis in D2 mice but not in B6 mice. In this study, we aimed to exhibit the difference in adipose tissue response in other areas, including interscapular brown adipose tissue (iBAT), inguinal white adipose tissue (ingWAT), and perigonadal WAT (perigoWAT) between resistant strain, B6 and susceptible strain, D2 after challenging them with M. pulmonis and SeV. Compared with B6 mice, D2 mice showed an increase in fat-associated lymphoid cluster in MFT, an increase in BAT in both iBAT and ingWAT after M. pulmonis and SeV infection. The results of this study indicate that pneumonia caused by M. pulmonis and SeV infection induces browning of adipocyte, suggesting that BAT plays a role in pathogen infection and inflammation.
  • Reduced translation efficiency due to novel splicing variants in 5' untranslated region and identification of novel cis-regulatory elements in canine and human BRCA2.
    Yasunaga Yoshikawa; Hajime Kozuma; Masami Morimatsu; Kaori Sugawara; Koichi Orino
    BMC molecular and cell biology, 22, 1, 2, 2, 06 Jan. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Breast cancer 2, early onset (BRCA2) is a tumor suppressor gene. The protein encoded by this gene plays an important role in homologous recombination (HR)-mediated DNA repair. Deleterious mutations in BRCA2 and downregulation of its expression have been associated with tumorigenesis in dogs and humans. Thus, regulation of BRCA2 expression level is important for maintaining homeostasis in homologous recombination. RESULTS: In this study, the mechanisms that regulate the expression of BRCA2 were proposed. Novel splicing variants were identified in the 5' untranslated region (UTR) of canine and human BRCA2 in canine testis, canine ovary, and canine and human cultured cell lines. In cultured cells, the ratio of BRCA2 splicing variants at the 5' UTR was altered by serum starvation. These novel splicing variants, excluding one of the canine splicing variants, were found to reduce the translational efficiency. Additionally, the DNA sequence in human BRCA2 intron 1 harbored novel cis-regulatory elements. Three silencer and two enhancer cis-regulatory elements were identified in human BRCA2 intron 1. CONCLUSIONS: This study demonstrates that BRCA2 expression level is regulated via 5' UTR splicing variants and that the BRCA2 intron 1 region harbors cis-regulatory elements.
  • Novel canine isocitrate dehydrogenase 1 mutation Y208C attenuates dimerization ability.
    Shota Kawakami; Masaki Michishita; Motoharu Sakaue; Masami Morimatsu; Mitsuki Uemura; Nobuaki Kashiwagi; Marika Maeda; Yukino Machida; Daigo Azakami; Ai S Egusa; Eri Onozawa; Katsumi Ishioka; Masami Watanabe; Yoshikazu Tanaka; Toshinori Omi; Kazuhiko Ochiai
    Oncology letters, 20, 6, 351, 351, Dec. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Isocitrate dehydrogenase 1 (IDH1) mutations are common in gliomas, acute myeloid leukemia, and chondrosarcoma. The mutation 'hotspot' is a single arginine residue, R132. The R132H mutant of IDH1 produces the 2-hydroxyglutarate (2-HG) carcinogen from α-ketoglutarate (α-KG). The reduction of α-KG induces the accumulation of hypoxia-inducible factor-1α subunit (HIF-1α) in the cytosol, which is a predisposing factor for carcinogenesis. R132H is the most common IDH1 mutation in humans, but mutations at the R132 residue can also occur in tumor tissues of dogs. The current study reported the discovery of a novel Tyr208Cys (Y208C) mutation in canine IDH1 (cIDH1), which was isolated from 2 of 45 canine chondrosarcoma cases. As the genomic DNA isolated from chondrosarcoma tissue was mutated, but that isolated from blood was not, Y208C mutations were considered to be spontaneous somatic mutations. The isocitrate dehydrogenase activity of the Y208C mutant was attenuated compared with that of wild-type (WT) cIDH1, but the attenuation of Y208C was less intense than that of the R132H mutation. The induction of HIF-1α response element activity and cell retention of HIF-1α were not increased by Y208C overexpression. In silico and cell biological analysis of IDH1 dimerization revealed that the Y208C mutation, but not the R132H mutation, attenuated binding activity with WT cIDH1. These data suggested that the attenuation of dimerization by the Y208C mutation may cause tumorigenesis through different mechanisms other than via 2-HG production by the IDH1 R132 mutation.
  • The canine RAD51 mutation leads to the attenuation of interaction with PALB2.
    Mitsuki Uemura; Kazuhiko Ochiai; Masami Morimatsu; Masaki Michishita; Eri Onozawa; Daigo Azakami; Yumiko Uno; Yasunaga Yoshikawa; Takanori Sasaki; Masami Watanabe; Toshinori Omi
    Veterinary and comparative oncology, 18, 2, 247, 255, Jun. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, RAD51 forms a complex with BRCA2 and plays a central role in the DNA damage response pathway that is associated with homologous recombination. The structures of RAD51 and its homologues are highly conserved from prokaryotes to higher eukaryotes. Although a large number of BRCA2 mutations have been reported, there are only a few reports on the mutations of RAD51, which have been shown in humans and dogs. However, several mutations of canine RAD51 were identified from mammary gland tumour tissues in a recent study. Some of these mutations seem to have an influence on the homo-oligomerization or interaction with "Partner and localizer of BRCA2" (PALB2). In this study, we cloned the canine PALB2 homologue and investigated the effect on its interaction with the RAD51 mutants to evaluate the alteration in the function of RAD51 mutants. The A209S and T225S mutants of RAD51 show an attenuation of the interaction between RAD51 and PALB2. These results indicate that the canine RAD51 mutations can potentially alter the homologous recombination pathways in response to DNA damage in dogs.
  • Profiling of cellular immune responses to Mycoplasma pulmonis infection in C57BL/6 and DBA/2 mice.
    Tussapon Boonyarattanasoonthorn; Yaser Hosny Ali Elewa; Hassan T Tag-El-Din-Hassan; Masami Morimatsu; Takashi Agui
    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 73, 55, 65, Sep. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Null mutation of the endothelin receptor type B gene causes embryonic death in the GK rat.
    Jinxi Wang; Ruihua Dang; Yoshiki Miyasaka; Kousuke Hattori; Daisuke Torigoe; Tadashi Okamura; Hassan T Tag-Ei-Din-Hassan; Masami Morimatsu; Tomoji Mashimo; Takashi Agui
    PloS one, 14, 6, e0217132, 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Analysis for genetic loci controlling protoscolex development in the Echinococcus multilocularis infection using congenic mice.
    Md Atiqul Islam; Daisuke Torigoe; Yayoi Kameda; Takao Irie; Hirokazu Kouguchi; Ryo Nakao; Md Abdul Masum; Osamu Ichii; Yasuhiro Kon; Hassan T Tag-El-Din-Hassan; Masami Morimatsu; Kinpei Yagi; Takashi Agui
    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 65, 65, 71, Nov. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The resistance/susceptibility to Echinococcus multilocularis infection in mice is genetically controlled. However, genetic factors responsible for these differences remain unknown. Our previous study in genetic linkage analysis has revealed that there is a significant quantitative trait locus (QTL) for the establishment of cyst (Emcys1), and a highly significant QTL for the development of protoscolex of E. multilocularis larvae (Empsc1), on mouse chromosomes 6 and 1, respectively. The current study aimed to confirm these QTLs and narrow down the critical genetic region that controls resistance/susceptibility to E. multilocularis infection by establishing congenic and subcongenic lines from C57BL/6 (B6) and DBA/2 (D2) mice. For protoscolex development phenotype, two congenic lines, B6.D2-Empsc1 and D2.B6-Empsc1 were developed, where responsible QTL, Empsc1 was introgressed from D2 into B6 background and vice versa. For cyst establishment phenotype, two congenic lines, B6.D2-Emcys1 and D2.B6-Emcys1 were developed, where responsible QTL, Emcys1 was introgressed from D2 into B6 background and vice versa. Because there was no significant difference in cyst establishment between B6.D2-Emcys1 and D2.B6-Emcys1 mice after challenge with E. multilocularis, it is suggested that the Emcys1 does not solely control the cyst establishment in mouse liver. However, infection experiments with B6.D2-Empsc1 and D2.B6-Empsc1 mice showed a significant difference in protoscolex development in the cyst. It confirms that the Empsc1 controls phenotype of the protoscolex development in the cyst. Subsequently, two subcongenic lines, B6.D2-Empsc1.1 and B6.D2-Empsc1.2 from B6.D2-Emcys1 and one subcongenic line, D2.B6-Empsc1.1 from D2.B6-Empsc1 were developed to narrow down the critical region responsible for protoscolex development. From the results of infection experiments with E. multilocularis in these subcongenic mice, it is concluded that a gene responsible for protoscolex development is located between D1Mit290 (68.1 cM) and D1Mit511 (97.3 cM).
  • Functional analysis of duck, goose, and ostrich 2'-5'-oligoadenylate synthetase.
    Hassan T Tag-El-Din-Hassan; Masami Morimatsu; Takashi Agui
    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 62, 220, 232, Elsevier B.V., Aug. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Endogenous Leu332Gln mutation in p53 disrupts the tetramerization ability in a canine mammary gland tumor cell line.
    Kazuhiko Ochiai; Daigo Azakami; Masami Morimatsu; Hinako Hirama; Shota Kawakami; Takayuki Nakagawa; Masaki Michishita; Ai S Egusa; Takanori Sasaki; Masami Watanabe; Toshinori Omi
    Oncology reports, 40, 1, 488, 494, Jul. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Mutations in the p53 gene are associated with more than half of all human cancers. These mutations often cause a disruption of the tumor-suppressor function of p53 and induce genomic instabilities. Wild‑type p53 requires tetramerization to function as an initiator of cell cycle arrest and apoptosis. Although alterations in p53 tetramerization caused by mutation have been well studied, there are few cell lines containing an endogenous mutation in the tetramerization domain of p53. Here, we report the discovery of a canine mammary gland tumor cell line CTB‑m2, which contains the Leu332Gln (L332Q) mutation corresponding to Leu344 in the tetramerization domain of human p53. Although CTB‑m2 cells are genetically heterozygous for the Leu332Gln mutation, the mutant mRNA was almost exclusively expressed. CTB‑m2 cells showed enhanced cell proliferation compared to wild‑type p53-expressing CTB‑m cells of the same lineage. A p53 tetramerization reporter assay showed that the ability of the p53 mutant to form tetramers was significantly lower than that of wild‑type p53. An immunoblot analysis of cross-linked p53 oligomerized forms demonstrated that the L332Q mutant lacked the ability to form tetramers but retained the ability to form dimers. These data suggest that the p53 mutant cell line CTB‑m2 could be a useful tool for analyzing the precise tetramerization mechanisms of p53 and verifying the effects of therapeutic agents against tumors expressing p53 mutants that lack the ability to tetramerize.
  • Immune cellular responses to sendai virus infection in D2.B6-Sen1Sen2Sen3 congenic mice, of which three quantitative trait loci responsible for the resistance to infection were introgressed from C57BL/6 mouse into DBA/2 mouse
    Raghda M. F. Abbas; Hassan T. Tag-El-Din-Hassan; Tussapon Boonyarattanasoonthorn; Keisuke Aoshima; Masami Morimatsu; Takashi Agui
    Japanese Journal of Veterinary Research, 66, 2, 93, 103, 01 May 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • R132 mutations in canine isocitrate dehydrogenase 1 (IDH1) lead to functional changes.
    Shota Kawakami; Kazuhiko Ochiai; Daigo Azakami; Yuiko Kato; Masaki Michishita; Masami Morimatsu; Toshina Ishiguro-Oonuma; Eri Onozawa; Masami Watanabe; Toshinori Omi
    Veterinary research communications, 42, 1, 49, 56, Mar. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Verification of genetic loci responsible for the resistance/susceptibility to the Sendai virus infection using congenic mice.
    Raghda Mohamed Fathi Abbas; Daisuke Torigoe; Yayoi Kameda; Hassan T Tag-El-Din-Hassan; Nobuya Sasaki; Masami Morimatsu; Takashi Agui
    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 57, 75, 81, Jan. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Comparison of the antiviral potential among soluble forms of herpes simplex virus type-2 glycoprotein D receptors, herpes virus entry mediator A, nectin-1 and nectin-2, in transgenic mice
    Yoshikazu Fujimoto; Yukiko Tomioka; Kinuyo Ozaki; Keiko Takeda; Haruka Suyama; Sayo Yamamoto; Hiroki Takakuwa; Masami Morimatsu; Toshimitsu Uede; Etsuro Ono
    JOURNAL OF GENERAL VIROLOGY, 98, 7, 1815, 1822, Jul. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Cell-cycle arrest in mature adipocytes impairs BAT development but not WAT browning, and reduces adaptive thermogenesis in mice
    Yuko Okamatsu-Ogura; Keigo Fukano; Ayumi Tsubota; Junko Nio-Kobayashi; Kyoko Nakamura; Masami Morimatsu; Hiroshi Sakaue; Masayuki Saito; Kazuhiro Kimura
    SCIENTIFIC REPORTS, 7, 1, 6648, Jul. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Canine REIC/Dkk-3 interacts with SGTA and restores androgen receptor signalling in androgen-independent prostate cancer cell lines
    Yuiko Kato; Kazuhiko Ochiai; Shota Kawakami; Nobuhiro Nakao; Daigo Azakami; Makoto Bonkobara; Masaki Michishita; Masami Morimatsu; Masami Watanabe; Toshinori Omi
    BMC VETERINARY RESEARCH, 13, 1, 170, Jun. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Analysis of the Relationship Between Enzymatic and Antiviral Activities of the Chicken Oligoadenylate Synthetase-Like
    Hassan T. Tag-El-Din-Hassan; Nobuya Sasaki; Daisuke Torigoe; Masami Morimatsu; Takashi Agui
    JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 37, 2, 71, 80, Feb. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • The role of mouse 2 ',5 '-oligoadenylate synthetase 1 paralogs
    Enas Elkhateeb; Hassan T. Tag-El-Din-Hassan; Nobuya Sasaki; Daisuke Torigoe; Masami Morimatsu; Takashi Agui
    INFECTION GENETICS AND EVOLUTION, 45, 393, 401, Nov. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • A soluble form of Siglec-9 provides a resistance against Group B Streptococcus (GBS) infection in transgenic mice
    Mitsumasa Saito; Sayo Yamamoto; Kinuyo Ozaki; Yukiko Tomioka; Haruka Suyama; Masami Morimatsu; Ken-ichi Nishijima; Shin-ichi Yoshida; Etsuro Ono
    MICROBIAL PATHOGENESIS, 99, 106, 110, Oct. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Cross-protective potential of anti-nucleoprotein human monoclonal antibodies against lethal influenza A virus infection
    Yoshikazu Fujimoto; Yukiko Tomioka; Hiroki Takakuwa; Gen-Ichiro Uechi; Toshiyo Yabuta; Kinuyo Ozaki; Haruka Suyama; Sayo Yamamoto; Masami Morimatsu; Le Quynh Mai; Tetsu Yamashiro; Toshihiro Ito; Koichi Otsuki; Etsuro Ono
    JOURNAL OF GENERAL VIROLOGY, 97, 9, 2104, 2116, Sep. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • A soluble form of human nectin-2 impairs exocrine secretion of pancreas and formation of zymogen granules in transgenic mice
    Yukiko Tomioka; Yoshikazu Fujimoto; Kanji Nakai; Kinuyo Ozaki; Sayo Yamamoto; Haruka Suyama; Masami Morimatsu; Toshihiro Ito; Etsuro Ono
    Biochemistry and Biophysics Reports, 5, 196, 202, Elsevier, 01 Mar. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Tumor suppressor REIC/DKK-3 and co-chaperone SGTA: Their interaction and roles in the androgen sensitivity
    Kazuhiko Ochiai; Masami Morimatsu; Yuiko Kato; Toshina Ishiguro-Oonuma; Chihiro Udagawa; Oumaporn Rungsuriyawiboon; Daigo Azakami; Masaki Michishita; Yuichi Ariyoshi; Hideo Ueki; Yasutomo Nasu; Hiromi Kumon; Masami Watanabe; Toshinori Omi
    ONCOTARGET, 7, 3, 3273, 3286, Jan. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Molecular cloning of canine co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA) and investigation of its ability to suppress androgen receptor signalling in androgen-independent prostate cancer
    Yuiko Kato; Kazuhiko Ochiai; Masaki Michishita; Daigo Azakami; Rei Nakahira; Masami Morimatsu; Toshina Ishiguro-Oonuma; Yasunaga Yoshikawa; Masato Kobayashi; Makoto Bonkobara; Masanori Kobayashi; Kimimasa Takahashi; Masami Watanabe; Toshinori Omi
    VETERINARY JOURNAL, 206, 2, 143, 148, Nov. 2015, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Nfkbiz regulates the proliferation and differentiation of keratinocytes
    Toshina Ishiguro-Oonuma; Kazuhiko Ochiai; Kazuyoshi Hashizume; Toshihiko Iwanage; Masami Morimatsu
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 63, 3, 107, 114, Aug. 2015, [Peer-reviewed]
    English, Scientific journal
  • Reduced canine BRCA2 expression levels in mammary gland tumors
    Yasunaga Yoshikawa; Masami Morimatsu; Kazuhiko Ochiai; Toshina Ishiguro-Oonuma; Seiichi Wada; Koichi Orino; Kiyotaka Watanabe
    BMC VETERINARY RESEARCH, 11, 159, Jul. 2015, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Identification of multiple genetic loci in the mouse controlling immobility time in the tail suspension and forced swimming tests
    Ahmed F. Abou-Elnaga; Daisuke Torigoe; Mohamed M. Fouda; Ragab A. Darwish; Usama A. Abou-Ismail; Masami Morimatsu; Takashi Agui
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 63, 2, 53, 62, May 2015, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • The role of IFN-gamma in regulating Nfkbiz expression in epidermal keratinocytes
    Toshina Ishiguro-Oonuma; Kazuhiko Ochiai; Kazuyoshi Hashizume; Masami Morimatsu
    BIOMEDICAL RESEARCH-TOKYO, 36, 2, 103, 107, Apr. 2015, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Polymorphisms of canine BRCA2 BRC repeats affecting interaction with RAD51
    Kazuhiko Ochiai; Toshina Ishiguro-Oonuma; Yasunaga Yoshikawa; Chihiro Udagawa; Yuiko Kato; Masami Watanabe; Makoto Bonkobara; Masami Morimatsu; Toshinori Omi
    BIOMEDICAL RESEARCH-TOKYO, 36, 2, 155, 158, Apr. 2015, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Hallmarks of Hepatitis C Virus in Equine Hepacivirus
    Tomohisa Tanaka; Hirotake Kasai; Atsuya Yamashita; Kaori Okuyama-Dobashi; Jun Yasumoto; Shinya Maekawa; Nobuyuki Enomoto; Toru Okamoto; Yoshiharu Matsuura; Masami Morimatsu; Noboru Manabe; Kazuhiko Ochiai; Kazuto Yamashita; Kohji Moriishi
    JOURNAL OF VIROLOGY, 88, 22, 13352, 13366, Nov. 2014, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor cells expressing MUC1 in transgenic mice
    Yukiko Tomioka; Masami Morimatsu; Ken-ichi Nishijima; Tatsufumi Usui; Sayo Yamamoto; Haruka Suyama; Kinuyo Ozaki; Toshihiro Ito; Etsuro Ono
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 450, 1, 532, 537, Jul. 2014, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Sensitization to laboratory animal allergens among students and researchers exposed to laboratory rodents in Hokkaido University
    Aya Yoshimura; Manabu Musashi; Takeaki Kaneko; Shunsuke Ohnishi; Chieko Orito; Yukako Kawahara; Satoshi Hashino; Masami Morimatsu; Satoshi Konno; Jiro Arikawa; Tetsuya Ishii; Masaya Sawamura; Ichiro Ueda
    Japanese Journal of Allergology, 63, 8, 1132, 1139, Japanese Society of Allergology, 2014, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • Abnormal spermatogenesis and reduced fertility in transgenic mice expressing the immediate-early protein IE180 of pseudorabies virus
    Yukiko Tomioka; Masami Morimatsu; Satoshi Taharaguchi; Sayo Yamamoto; Haruka Suyama; Kinuyo Ozaki; Naoki Iwamori; Etsuro Ono
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 440, 4, 683, 688, Nov. 2013, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Molecular cloning and tumour suppressor function analysis of canine REIC/Dkk-3 in mammary gland tumours
    Kazuhiko Ochiai; Masami Watanabe; Daigo Azakami; Masaki Michishita; Yasunaga Yoshikawa; Chihiro Udagawa; Pornphimon Metheenukul; Thippayarat Chahomchuen; Hiroshi Aoki; Hiromi Kumon; Masami Morimatsu; Toshinori Omi
    VETERINARY JOURNAL, 197, 3, 769, 775, Sep. 2013, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • I kappa B zeta Is a Transcriptional Key Regulator of CCL2/MCP-1
    Dominic G. Hildebrand; Eva Alexander; Sebastian Hoerber; Simon Lehle; Kerstin Obermayer; Niels-Arne Muenck; Oliver Rothfuss; Julia-Stefanie Frick; Masami Morimatsu; Ingo Schmitz; Johannes Roth; Jan M. Ehrchen; Frank Essmann; Klaus Schulze-Osthoff
    JOURNAL OF IMMUNOLOGY, 190, 9, 4812, 4820, May 2013, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
    English, Scientific journal
  • Effects of the Missense Mutations in Canine BRCA2 on BRC Repeat 3 Functions and Comparative Analyses between Canine and Human BRC Repeat 3
    Yasunaga Yoshikawa; Kazuhiko Ochiai; Masami Morimatsu; Yu Suzuki; Seiichi Wada; Takahiro Taoda; Satomi Iwai; Seishiro Chikazawa; Koichi Orino; Kiyotaka Watanabe
    PLOS ONE, 7, 10, e45833, Oct. 2012, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Molecular epidemiology of avian influenza viruses circulating among healthy poultry flocks in farms in northern Vietnam
    Hiroki Takakuwa; Tetsu Yamashiro; Mai Q. Le; Lien S. Phuong; Hiroichi Ozaki; Ryota Tsunekuni; Tatsufumi Usui; Hiroshi Ito; Masami Morimatsu; Yukiko Tomioka; Tsuyoshi Yamaguchi; Toshihiro Ito; Toshiyuki Murase; Etsuro Ono; Koichi Otsuki
    PREVENTIVE VETERINARY MEDICINE, 103, 2-3, 192, 200, Feb. 2012, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Establishment of a PCR analysis method for canine BRCA2
    Yasunaga Yoshikawa; Masami Morimatsu; Kazuhiko Ochiai; Kento Okuda; Takahiro Taoda; Seishiro Chikazawa; Asako Shimamura; Toshinori Omi; Makoto Bonkobara; Koichi Orino; Kiyotaka Watanabe
    BMC Research Notes, 5, 173, 182, 2012, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Interactions between canine RAD51 and full length or truncated BRCA2 BRC repeats
    K. Ochiai; Y. Yoshikawa; T. Oonuma; Y. Tomioka; K. Hashizume; M. Morimatsu
    VETERINARY JOURNAL, 190, 2, 293, 295, Nov. 2011, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • A nucleoside anticancer drug, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (TAS106), sensitizes cells to radiation by suppressing BRCA2 expression
    Shunsuke Meike; Tohru Yamamori; Hironobu Yasui; Masato Eitaki; Akira Matsuda; Masami Morimatsu; Masakazu Fukushima; Yasundo Yamasaki; Osamu Inanami
    MOLECULAR CANCER, 10, 92, 100, Jul. 2011, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Valine 1532 of human BRC repeat 4 plays an important role in the interaction between BRCA2 and RAD51
    Kazuhiko Ochiai; Yasunaga Yoshikawa; Kumiko Yoshimatsu; Toshina Oonuma; Yukiko Tomioka; Eichi Takeda; Jiro Arikawa; Katsumi Mominoki; Toshinori Omi; Kazuyoshi Hashizume; Masami Morimatsu
    FEBS LETTERS, 585, 12, 1771, 1777, Jun. 2011, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Motor-Coordination-Dependent Learning, More than Others, Is Impaired in Transgenic Mice Expressing Pseudorabies Virus Immediate-Early Protein IE180
    Juan C. Lopez-Ramos; Yukiko Tomioka; Masami Morimatsu; Sayo Yamamoto; Kinuyo Ozaki; Etsuro Ono; Jose M. Delgado-Garcia
    PLOS ONE, 5, 8, e12123, Aug. 2010, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Discoidin Domain Receptor 2 (DDR2) Is Required for Maintenance of Spermatogenesis in Male Mice
    Kiyoshi Kano; Ayami Kitamura; Takashi Matsuwaki; Masami Morimatsu; Kunihiko Naito
    MOLECULAR REPRODUCTION AND DEVELOPMENT, 77, 1, 29, 37, Jan. 2010, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Fusion protein consisting of the first immunoglobulin-like domain of porcine nectin-1 and Fc portion of human IgG1 provides a marked resistance against pseudorabies virus infection to transgenic mice
    Yukiko Tomioka; Masami Morimatsu; Keiko Amagai; Minako Kuramochi; Yuki Watanabe; Shigeto Kouda; Toshio Wada; Noritaka Kuboki; Etsuro Ono
    MICROBIOLOGY AND IMMUNOLOGY, 53, 1, 8, 15, Jan. 2009, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Novel variations and loss of heterozygosity of BRCA2 identified in a dog with mammary tumors
    Yasunaga Yoshikawa; Masami Morimatsu; Kazuhiko Ochiai; Masashi Nagano; Yukiko Tomioka; Nobuo Sasaki; Kazuyoshi Hashizume; Toshihiko Iwanaga
    AMERICAN JOURNAL OF VETERINARY RESEARCH, 69, 10, 1323, 1328, Oct. 2008, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Microphthalmia and lack of vitreous body in transgenic mice expressing the first immunoglobulin-like domain of nectin-1
    Kazuhiko Yoshida; Yukiko Tomioka; Satoru Kase; Masami Morimatsu; Kyoko Shinya; Shigeaki Ohno; Etsuro Ono
    GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 246, 4, 543, 549, Apr. 2008, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Cerebellar pathology in transgenic mice expressing the pseudorabies virus immediate-early protein IE180
    Yukiko Tomioka; Taisuke Miyazaki; Satoshi Taharaguchi; Saori Yoshino; Masami Morimatsu; Toshimitsu Uede; Etsuro Ono; Masahiko Watanabe
    EUROPEAN JOURNAL OF NEUROSCIENCE, 27, 8, 2115, 2132, Apr. 2008, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Comparison of the antiviral potentials among the pseudorabies-resistant transgenes encoding different soluble forms of porcine nectin-1 in transgenic mice
    Etsuro Ono; Yukiko Tomioka; Yuki Watanabe; Keiko Amagai; Masami Morimatsu; Kyoko Shinya; Pierre Cherel
    JOURNAL OF GENERAL VIROLOGY, 88, Pt 10, 2636, 2641, Oct. 2007, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Role of NF-kappa B in constitutive expression of MAIL in epidermal keratinocytes
    Toshina Oonuma; Masami Morimatsu; Kazuhiko Ochiai; Toshihiko Iwanaga; Kazuyoshi Hashizume
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 69, 3, 279, 284, Mar. 2007, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Immunohistochemical and in situ hybridization analysis of galectin-3, a beta-galactoside binding lectin, in the urinary system of adult mice
    Junko Nio; Hiromi Takahashi-Iwanaga; Masami Morimatsu; Yasuhiro Kon; Toshihiko Iwanaga
    HISTOCHEMISTRY AND CELL BIOLOGY, 126, 1, 45, 56, Jul. 2006, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Spermatogonial cell-mediated activation of an I kappa B zeta-independent nuclear factor-kappa B pathway in sertoli cells induces transcription of the Lipocalin-2 gene
    RS Fujino; K Tanaka; M Morimatsu; K Tamura; H Kogo; T Hara
    MOLECULAR ENDOCRINOLOGY, 20, 4, 904, 915, Apr. 2006, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Elevated plasma concentrations of haptoglobin in European brown bears during hibernation
    K Mominoki; M Morimatsu; M Kaijalainen; E Hohtola; R Hissa; M Saito
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY, 142, 4, 472, 477, Dec. 2005, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Analysis of genetic variations in the exon 27 region of the canine BRCA2 locus
    Y Yoshikawa; M Morimatsu; K Ochiai; M Nagano; Y Yamane; N Tomizawa; N Sasaki; K Hashizume
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 67, 10, 1013, 1017, Oct. 2005, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Histochemical demonstration of a Na+-coupled transporter for short-chain fatty acids (Slc5a8) in the intestine and kidney of the mouse
    Kumiko Takebe; Junko Nio; Masami Morimatsu; Shin-Ichiro Karaki; Atsukazu Kuwahara; Ikuo Kato; Toshihiko Iwanaga
    BIOMEDICAL RESEARCH-TOKYO, 26, 5, 213, 221, Oct. 2005, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Insertion/deletion polymorphism in the BRCA2 nuclear localization signal
    Y Yoshikawa; M Morimatsu; K Ochiai; M Nagano; Y Yamane; N Tomizawa; N Sasaki; K Hashizume
    BIOMEDICAL RESEARCH-TOKYO, 26, 3, 109, 116, Jun. 2005, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Targeted disruption of MAIL, a nuclear I kappa B protein, leads to severe atopic dermatitis-like disease
    T Shiina; A Konno; T Oonuma; H Kitamura; K Imaoka; N Takeda; K Todokoro; M Morimatsu
    JOURNAL OF BIOLOGICAL CHEMISTRY, 279, 53, 55493, 55498, Dec. 2004, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Brca2 C-terminus interacts with Rad51 and contributes to nuclear focus formation in double-strand break repair of DNA
    K Ochiai; M Morimatsu; Y Yoshikawa; B Syuto; K Hashizume
    BIOMEDICAL RESEARCH-TOKYO, 25, 6, 269, 275, Dec. 2004, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Transcriptional regulation of the MAIL gene in LPS-stimulated RAW264 mouse macrophages
    T Ito; M Morimatsu; T Oonuma; T Shiina; H Kitamura; B Syuto
    GENE, 342, 1, 137, 143, Nov. 2004, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Cloning of bovine MAIL and its mRNA expression in white blood cells of Holstein cows
    D Yamaji; H Kitamura; K Kimura; Y Matsushita; H Okada; T Shiina; M Morimatsu; M Saito
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 98, 3-4, 175, 184, Apr. 2004, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules
    BH Lee; K Yoshimatsu; A Maeda; K Ochiai; M Morimatsu; K Araki; M Ogino; S Morikawa; J Arikawa
    VIRUS RESEARCH, 98, 1, 83, 91, Dec. 2003, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Properties of the tumor suppressor gene Brca2 in the cat
    T Oonuma; M Morimatsu; K Ochiai; B Syuto
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 65, 10, 1123, 1126, Oct. 2003, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Role of CXCR4 and SDF-1 in mammary tumor metastasis in the cat
    T Oonuma; M Morimatsu; T Nakagawa; R Uyama; N Sasaki; M Nakaichi; H Tamamura; N Fuji; S Hashimoto; H Yamamura; B Syuto
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 65, 10, 1069, 1073, Oct. 2003, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Bacterial lipopolysaccharide-induced expression of the I kappa B protein MAIL in B-lymphocytes and macrophages
    H Kitamura; Y Matsushita; T Iwanaga; K Mori; K Kanehira; D Fujikura; M Morimatsu; M Saito
    ARCHIVES OF HISTOLOGY AND CYTOLOGY, 66, 1, 53, 62, Mar. 2003, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • The multimerization of hantavirus nucleocapsid protein depends on type-specific epitopes
    K Yoshimatsu; BH Lee; K Araki; M Morimatsu; M Ogino; H Ebihara; J Arikawa
    JOURNAL OF VIROLOGY, 77, 2, 943, 952, Jan. 2003, [Peer-reviewed], [International Magazine]
    English
  • Cellular expression of gut chitinase mRNA in the gastrointestinal tract of mice and chickens
    M Suzuki; W Fujimoto; M Goto; M Morimatsu; B Syuto; T Iwanaga
    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 50, 8, 1081, 1089, Aug. 2002, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Characterization of binding sites for diisopropyl phosphorofluoridate in spinal cord cytosol
    R Kamata; M Morimatsu; T Suzuki; T Takewaki; H Kobayashi
    ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, 12, 1, 55, 58, Aug. 2002, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • The identification and properties of chitin-binding protein b01 (CBPb01)
    M Suzuki; M Morimatsu; B Syuto
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 64, 6, 477, 481, Jun. 2002, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Bacterial lipopolysaccharide induces mRNA expression of an I kappa B MAIL through toll-like receptor 4
    H Kitamura; K Kanehira; T Shiina; M Morimatsu; BD Jung; S Akashi; M Saito
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 64, 5, 419, 422, May 2002, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • A novel serum chitinase that is expressed in bovine liver
    M Suzuki; M Morimatsu; T Yamashita; T Iwanaga; B Syuto
    FEBS LETTERS, 506, 2, 127, 130, Oct. 2001, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Genomic organization, chromosomal localization, and promoter analysis of the mouse Mail gene
    T Shiina; M Morimatsu; H Kitamura; T Ito; S Kidou; K Matsubara; Y Matsuda; M Saito; B Syuto
    IMMUNOGENETICS, 53, 8, 649, 655, Oct. 2001, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Cloning and sequencing full length of canine Brca2 and Rad51 cDNA
    K Ochiai; M Morimatsu; N Tomizawa; B Syuto
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 63, 10, 1103, 1108, Oct. 2001, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Changes in sodium or glucose filtration rate modulate expression of glucose transporters in renal proximal tubular cells of rat
    S Vestri; MM Okamoto; HS de Freitas; RA dos Santos; MT Nunes; M Morimatsu; JC Heimann; UF Machado
    JOURNAL OF MEMBRANE BIOLOGY, 182, 2, 105, 112, Jul. 2001, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Isolation, characterization, and cDNA cloning of chicken turpentine-induced protein, a new member of the scavenger receptor cysteine-rich (SRCR) family of proteins
    K Iwasaki; M Morimatsu; O Inanami; E Uchida; B Syuto; M Kuwabara; M Niiyama
    JOURNAL OF BIOLOGICAL CHEMISTRY, 276, 12, 9400, 9405, Mar. 2001, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • MAIL, a novel nuclear I kappa B protein that potentiates LPS-induced IL-6 production
    H Kitamura; K Kanehira; K Okita; M Morimatsu; M Saito
    FEBS LETTERS, 485, 1, 53, 56, Nov. 2000, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • The evaluation of the potential of botulinum C3 enzyme as an exogenous differentiation inducing factor to neurons
    Y Watanabe; M Morimatsu; B Syuto
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 62, 5, 473, 478, May 2000, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Canine leptin: cDNA cloning, expression and activity of recombinant protein
    M Iwase; K Kimura; N Sasaki; R Komagome; K Ishioka; M Morimatsu; T Murakami; M Saito
    RESEARCH IN VETERINARY SCIENCE, 68, 2, 109, 114, Apr. 2000, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Botulinum C3 enzyme changes the lactate dehydrogenase isozyme pattern of primary culture of neurons
    Y Watanabe; M Morimatsu; B Syuto
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 62, 3, 249, 254, Mar. 2000, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Mutated human beta 3-adrenergic receptor (Trp64Arg) lowers the response to beta 3-adrenergic agonists in transfected 3T3-L1 preadipocytes
    K Kimura; N Sasaki; A Asano; J Mizukami; S Kayahashi; T Kawada; T Fushiki; M Morimatsu; T Yoshida; M Saito
    HORMONE AND METABOLIC RESEARCH, 32, 3, 91, 96, Mar. 2000, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Cells deleted for Brca2 COOH terminus exhibit hypersensitivity to gamma-radiation and premature senescence
    M Morimatsu; G Donoho; P Hasty
    CANCER RESEARCH, 58, 15, 3441, 3447, Aug. 1998, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Comparison of amino acid sequence of the C-terminal domain of insulin-responsive glucose transporter (GLUT4) in livestock mammals
    H Abe; Y Kawakita; T Miyashige; M Morimatsu; M Saito
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 60, 6, 769, 771, Jun. 1998, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Central IL-1 differentially regulates peripheral IL-6 and TNF synthesis
    H Kitamura; S Okamoto; Y Shimamoto; M Morimatsu; A Terao; M Saito
    CELLULAR AND MOLECULAR LIFE SCIENCES, 54, 3, 282, 287, Mar. 1998, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Adrenergic activation of vascular endothelial growth factor mRNA expression in rat brown adipose tissue: implication in cold-induced angiogenesis
    A Asano; M Morimatsu; H Nikami; T Yoshida; M Saito
    BIOCHEMICAL JOURNAL, 328, 179, 183, Nov. 1997, [Peer-reviewed], [International Magazine]
    English
  • Immobilization stress increases hepatic IL-6 expression in mice
    H Kitamura; A Konno; M Morimatsu; BD Jung; K Kimura; M Saito
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 238, 3, 707, 711, Sep. 1997, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2
    SK Sharan; M Morimatsu; U Albrecht; DS Lim; E Regel; C Dinh; A Sands; G Eichele; P Hasty; A Bradley
    NATURE, 386, 6627, 804, 810, Apr. 1997, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Molecular cloning and mRNA expression of the bovine insulin-responsive glucose transporter (GLUT4)
    H Abe; M Morimatsu; H Nikami; T Miyashige; M Saito
    JOURNAL OF ANIMAL SCIENCE, 75, 1, 182, 188, Jan. 1997, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Seasonal variations of blood haptoglobin level of brown bears in Japan
    K Mominoki; H Tsuruga; M Morimatsu; M Saito
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-PHYSIOLOGY, 114, 4, 349, 353, Aug. 1996, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Expression and localization of insulin-regulatable glucose transporter (GLUT4) in rat brain
    M Kobayashi; H Nikami; M Morimatsu; M Saito
    NEUROSCIENCE LETTERS, 213, 2, 103, 106, Aug. 1996, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Seasonal variations of blood haptoglobin level of brown bears in Japan.
    K Mominoki; H Tsuruga; M Morimatsu; M Saito
    Comparative biochemistry and physiology. Part A, Physiology, 114, 4, 349, 53, Aug. 1996, [International Magazine]
    English, Scientific journal, Haptoglobin (Hp), a hemoglobin-binding protein, is known as an acute phase protein increasing in blood during inflammation in most mammals. On the basis of our previous studies on purification and characterization of bear Hp (Comp. Biochem. Physiol. 110B, 785-789, 1995), in this study, we developed an immunoassay method to measure serum Hp level in bear, and measured the concentration of Hp in blood samples collected from 84 reared and 25 wild brown bears in Hokkaido, Japan. The mean serum Hp concentration was 0.94 +/- 0.25 mg/ml in wild bears, which is nearly equal to those reported in other species. In reared bears, the Hp concentration was apparently higher (3.82 +/- 0.29 mg/ml), although total protein and albumin concentrations were nearly equal in the two groups. A significant seasonal variation of serum Hp, low in spring and high in autumn and winter, was found in reared bears. Possible factors participating in the seasonal variation were discussed with special references to hibernation.
  • PLASMA HAPTOGLOBIN RESPONSE TO INTRACEREBROVENTRICULAR ADMINISTRATION OF CYTOKINES IN RATS
    H KITAMURA; Y SHIMAMOTO; M MORIMATSU; A TERAO; M SAITO
    BIOMEDICAL RESEARCH-TOKYO, 16, 5, 353, 356, Oct. 1995, [Peer-reviewed], [International Magazine]
    English
  • STIMULATION OF HAPTOGLOBIN SYNTHESIS BY INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR, BUT NOT BY INTERLEUKIN-1, IN BOVINE PRIMARY CULTURED-HEPATOCYTES
    N NAKAGAWATOSA; M MORIMATSU; M KAWASAKI; H NAKATSUJI; B SYUTO; M SAITO
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 57, 2, 219, 223, Apr. 1995, [Peer-reviewed], [International Magazine]
    English
  • HAPTOGLOBIN IN CARNIVORA - A UNIQUE MOLECULAR-STRUCTURE IN BEAR, CAT AND DOG HAPTOGLOBINS
    K MOMINOKI; N NAKAGAWATOSA; M MORIMATSU; B SYUTO; M SAITO
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY, 110, 4, 785, 789, Apr. 1995, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Haptoglobin in Carnivora: a unique molecular structure in bear, cat and dog haptoglobins.
    K Mominoki; N Nakagawa-Tosa; M Morimatsu; B Syuto; M Saito
    Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, 110, 4, 785, 9, Apr. 1995, [International Magazine]
    English, Scientific journal, Haptoglobin (Hp), a hemoglobin-binding protein in plasma, consists of alpha and beta subunits and has a tetra-chain arrangement (beta-alpha-alpha-beta) connected by disulfide bridges in most mammals so far examined. Dog Hp has been reported to be unique compared with other Hps in respect that (1) the two alpha beta units are joined by a non-covalent interaction rather than a disulfide bridge and (2) the alpha chain has an oligosaccharide-binding sequence (Asn-X-Ser/Thr) and is glycosylated. To determine whether the unique structures of dog Hp are common in the Carnivora, we purified Hps from sera of bear and cat, and analyzed their subunit structure and partial amino acid sequences. The analyses by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, under both reducing and non-reducing conditions, revealed that bear and cat Hps have similar subunit arrangements to dog Hp, suggesting the absence of a disulfide bridge between two alpha chains. This was confirmed by amino acid sequence analysis of the alpha chains: that is, Cys15 participating in the inter-alpha chain disulfide bridge was replaced by Val in bear or Leu in cat and dog. Thus, the unique subunit arrangement of Hp reported in dog may be common in the Carnivora. In contrast to dog Hp, however, alpha chains of bear and cat Hps were found not to have the typical oligosaccharide binding sequence on their alpha chains and were not glycosylated.
  • HYPERPLASIA OF BROWN ADIPOSE-TISSUE AFTER CHRONIC STIMULATION OF BETA-3-ADRENERGIC RECEPTOR IN RATS
    NAGASE, I; N SASAKI; K TSUKAZAKI; T YOSHIDA; M MORIMATSU; M SAITO
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 42, 3-4, 137, 146, Dec. 1994, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • ISOLATION AND PRIMARY CULTURE OF BOVINE HEPATOCYTES - ALBUMIN SYNTHESIS AND ADRENERGIC ACTIVATION OF GLYCOGENOLYSIS
    N NAKAGAWATOSA; M MORIMATSU; K MOMINOKI; H NAKATSUJI; B SYUTO; M SAITO
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 56, 1, 125, 129, Feb. 1994, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • AVIDITY OF ANTIBODY AND AGGLUTINABILITY OF ANTIBODY-SENSITIZED LATEX IN LATEX AGGLUTINATION-TEST
    S YAMAMOTO; K TAGATA; Y ISHIKAWA; H SANTSUKA; M YAMADA; M MORIMATSU; M NAIKI
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 36, 3, 257, 264, Apr. 1993, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • EFFICIENT PREPARATION OF MONOSPECIFIC ANTI-CANINE C-REACTIVE PROTEIN SERUM AND PURIFICATION OF CANINE C-REACTIVE PROTEIN BY AFFINITY-CHROMATOGRAPHY
    S YAMAMOTO; N ABE; H SANTSUKA; T SHIDA; K KISHIDA; S KUWAJIMA; M YAMADA; M MORIMATSU; M NAIKI
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 36, 3, 293, 301, Apr. 1993, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • PURIFICATION AND IDENTIFICATION OF A SERUM-PROTEIN INCREASED BY ANTHELMINTIC DRUGS FOR DIROFILARIA-IMMITIS IN DOGS
    N TOSA; M MORIMATSU; M NAKAGAWA; F MIYOSHI; E UCHIDA; M NIIYAMA; B SYUTO; M SAITO
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 55, 1, 27, 31, Feb. 1993, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • INDUCTION OF ACUTE PHASE PROTEIN BY RECOMBINANT HUMAN INTERLEUKIN-6 (IL-6) IN CALVES
    Y NAKAJIMA; E MOMOTANI; T MURAKAMI; Y ISHIKAWA; M MORIMATSU; M SAITO; H SUZUKI; K YASUKAWA
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 35, 3-4, 385, 391, Jan. 1993, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • BOVINE HAPTOGLOBIN - SINGLE RADIAL IMMUNODIFFUSION ASSAY OF ITS POLYMERIC FORMS AND DRAMATIC RISE IN ACUTE-PHASE SERA
    M MORIMATSU; M SARIKAPUTI; B SYUTO; M SAITO; S YAMAMOTO; M NAIKI
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 33, 4, 365, 372, Sep. 1992, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • PREPARATION OF LATEX SENSITIZED WITH RABBIT IGG ANTIBODY FOR SLIDE REVERSED PASSIVE AGGLUTINATION
    S YAMAMOTO; K TAGATA; Y ISHIKAWA; H FUJISE; H NAGAHATA; M YAMADA; T SAKANO; M MORIMATSU; M NAIKI
    VETERINARY RESEARCH COMMUNICATIONS, 16, 4, 265, 272, Aug. 1992, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • LATEX AGGLUTINATION-TEST - A SIMPLE, RAPID AND PRACTICAL METHOD FOR BOVINE SERUM CRP DETERMINATION
    M SARIKAPUTI; M MORIMATSU; S YAMAMOTO; B SYUTO; M SAITO; M NAIKI
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 40, 1, 1, 12, May 1992, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • ISOLATION OF C-REACTIVE PROTEIN FROM CAT SERUM
    A WATANABE; M MORIMATSU; K YOSHIMATSU; S YAMAMOTO; A TERAO; K TSUKAZAKI; M SAITO; M NAIKI
    JOURNAL OF SMALL ANIMAL PRACTICE, 33, 2, 71, 77, Feb. 1992, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • ISOLATION OF CANINE C-REACTIVE PROTEIN AND CHARACTERIZATION OF ITS PROPERTIES
    S YAMAMOTO; K TAGATA; H NAGAHATA; Y ISHIKAWA; M MORIMATSU; M NAIKI
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 30, 4, 329, 339, Jan. 1992, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • ELEVATION OF BOVINE SERUM C-REACTIVE PROTEIN AND SERUM AMYLOID-P COMPONENT LEVELS BY LACTATION
    M MORIMATSU; A WATANABE; K YOSHIMATSU; T FUJINAGA; M OKUBO; M NAIKI
    JOURNAL OF DAIRY RESEARCH, 58, 3, 257, 261, Aug. 1991, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • ISOLATION AND CHARACTERIZATION OF BOVINE HAPTOGLOBIN FROM ACUTE PHASE SERA
    M MORIMATSU; B SYUTO; N SHIMADA; T FUJINAGA; S YAMAMOTO; M SAITO; M NAIKI
    JOURNAL OF BIOLOGICAL CHEMISTRY, 266, 18, 11833, 11837, Jun. 1991, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • A NEW PURIFICATION PROCEDURE FOR BOVINE C-REACTIVE PROTEIN AND SERUM AMYLOID-P COMPONENT
    M SARIKAPUTI; M MORIMATSU; B SYUTO; M SAITO; M NAIKI
    INTERNATIONAL JOURNAL OF BIOCHEMISTRY, 23, 10, 1137, 1142, 1991, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • ISOLATION AND CHARACTERIZATION OF C-REACTIVE PROTEIN AND SERUM AMYLOID-P COMPONENT FROM BOVINE SERUM
    M MORIMATSU; H SAKAI; K YOSHIMATSU; O MINOWA; S YAMAMOTO; K YATOMI; T FUJINAGA; M NAIKI
    JAPANESE JOURNAL OF VETERINARY SCIENCE, 51, 4, 723, 732, Aug. 1989, [Peer-reviewed], [International Magazine]
    English, Scientific journal
■ Other Activities and Achievements
■ Syllabus
  • アドバンスト演習, 2024年, 学士課程, 獣医学部
  • Human-Animal Bond and One Health 特別科目群, 2024年, 博士後期課程, 獣医学院
  • 獣医科学特別研究, 2024年, 博士後期課程, 獣医学院
  • Human-Animal Bond and One Health 特別科目群, 2024年, 博士後期課程, 国際感染症学院
  • 獣医科学特論演習, 2024年, 博士後期課程, 獣医学院
  • 研究倫理演習, 2024年, 博士後期課程, 獣医学院
  • 研究倫理演習, 2024年, 博士後期課程, 国際感染症学院
  • 実験動物学特論, 2024年, 博士後期課程, 獣医学院
  • 獣医学専門セミナーⅠ, 2024年, 学士課程, 獣医学部
  • 獣医学専門セミナーⅡ, 2024年, 学士課程, 獣医学部
  • アドバンスト演習, 2024年, 学士課程, 獣医学部
  • アドバンスト演習, 2024年, 学士課程, 獣医学部
  • 実験動物学・獣医遺伝学, 2024年, 学士課程, 獣医学部
  • 実験動物学実習, 2024年, 学士課程, 獣医学部
■ Affiliated academic society
  • JAPANESE ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
  • THE JAPANESE BIOCHEMICAL SOCIETY
  • THE MOLECULAR BIOLOGY SOCIETY OF JAPAN
  • THE JAPANESE SOCIETY OF VETERINARY SCIENCE
  • The Japanese College of Laboratory Animal Medicine (JCLAM)
  • The Japanese Association for Laboratory Animal Medicine (JALAM)
■ Research Themes
  • DNA損傷を誘導する抗がん剤による心機能障害への対策を目指したNFKBIZの機能解明
    科学研究費助成事業
    01 Apr. 2025 - 31 Mar. 2028
    森松 正美
    日本学術振興会, 基盤研究(C), 北海道大学, 25K09450
  • キヌレニン経路関連遺伝子改変マウスを用いたキヌレン酸多機能誘導体による新薬開発
    二国間交流事業
    Apr. 2026 - Mar. 2028
    森松正美、池中良徳、富岡幸子、大竹正剛、小野悦郎、清水真魚、橋爪 花
    独立行政法人日本学術振興会, ハンガリー(MTA)との共同研究, Principal investigator, 120263801
  • NFkB情報伝達系が癌発症に及ぼす影響におけるNFKBIZの機能解明
    科学研究費助成事業
    Apr. 2022 - Mar. 2025
    森松 正美
    日本学術振興会, 基盤研究(C), 北海道大学, 22K05998
  • 感受性責任遺伝子探索による多包虫症の寄生体・宿主相互作用の分子機序の解明
    科学研究費助成事業
    Apr. 2020 - Mar. 2023
    安居院 高志; 野中 成晃; 森松 正美; 八木 欣平
    本研究は多包虫（エキノコックス）感染に置いて嚢胞内に原頭節を有する感受性の系統（DBA/2 (D2) ）と原頭節を有さない抵抗性の系統（C57BL/6 (B6)）が存在することから、原頭節の有無を制御している原因を明らかにすることである。昨年度までにB6を遺伝的背景にD2由来の染色体断片に入れ替えた（サブ）コンジェニックマウスを用いてエキノコックス感染実験を行った結果、責任遺伝子の存在領域を3.3 cMまで狭めることができた。この範囲内には55個の遺伝子が存在していた。候補領域内の全遺伝子55個について別の研究で作成されたRNAseqのデータを参照しSNPの有無を確認すると、34個の遺伝子においてB6とD2との間でSNPが存在していた。この34個についてEnsemblデータベースを利用しアミノ酸置換を伴っているかを確認したところ21個の遺伝子でアミノ酸置換が確認できた。D2-B6間で翻訳領域にアミノ酸置換が見られる遺伝子は10個であった。従ってこの10個の遺伝子の中に責任遺伝子が存在する可能性が示唆された。これら10個についてB6、D2、BALB/c、AKRの4つのマウス系統でSNPを比較した。その結果ある遺伝子にのみD2特異的なSNPが確認された。この遺伝子はある酵素をコードするものであった。そこでこの遺伝子をB6及びD2マウスより単離し、これを発現ベクターに組み込み、それを線維芽細胞株にトランスフェクトしその酵素活性の違いを検討した。しかし、酵素活性の測定方法の確立に時間を要し未だ結論を得ない状況である。
    日本学術振興会, 基盤研究(C), 北海道大学, 20K06407
  • 腫瘍におけるBRCA２の変異と結合分子群の機能解明を目的とした新規モデルの作出
    科学研究費補助金（基盤研究(B)）
    2018 - 2021
    森松 正美
    日本学術振興会, Principal investigator, Competitive research funding
  • Anti-tumor mechanism of soluble form of sialic acid-recognizing protein, Siglec-9
    Grants-in-Aid for Scientific Research
    Apr. 2014 - Mar. 2017
    Tomioka Yukiko; TAKEUCHI Takashi
    It was revealed that proliferation and malignant transformation of MUC1-positive tumor were prevented in the transgenic mice expressing a soluble form of sialic acid-binding immunoglobulin-like lectin 9 (sSiglec-9). In addition, it was suggested that this anti-tumor mechanism indirectly acted through the immune system of the host. On the other hand, sSiglec-9 acivated a proliferation of MUC16-positive tumor rather than inhibited, surprisingly. According to the above results, it was shown Siglec-9 interacted with the mucin expressed in tumor and to participate in a tumor proliferation and malignant transformation. These knowledge make the beginning to found the molecular targeted therapy for cancers through Siglec-9.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Tottori University, 26450398
  • 組換え酵素Rad51と癌抑制タンパク質BRCA2の結合の種間比較に基づく分子創薬
    科学研究費補助金（基盤研究(C)）
    2014 - 2016
    森松 正美
    日本学術振興会, Principal investigator, Competitive research funding
  • Mechanisms of development of AIDS encephalopathy using a new transgenic mouse model expressing HIV-1 Nef
    Grants-in-Aid for Scientific Research
    Apr. 2012 - Mar. 2014
    TOMIOKA Yukiko; ONO Etsuro; MORIMATSU Masami
    Transgenic mice expressing Human Immunodeficiency Virus 1 (HIV-1) accessory protein Nef (Nef Tg) showed the severe neurological symptom including motor ataxia, hindquarter paralysis, and epileptic seizure. Histopathologically, prominent astrocytosis, microgliosis, vacuolation of the white matter, lymphocytic infiltration were observed in the brain and spinal cord of Nef Tg. In addition, expression of some cytokines such as IP-10 was increased in the brain of Nef Tg. These pathological changes were similar to those of AIDS encephalopathy in human, which indicated that Nef protein plays an important role in neuropathogenesis of HIV-1 infection.
    Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, 24780280
  • Tumorigenic effects of BRCA2 mutation and genomic instability in dogs
    Grants-in-Aid for Scientific Research
    2011 - 2013
    MORIMATSU Masami; OCHIAI Kazuhiko
    Mammary tumors are the most common tumor type in both human and canine females. In women, carriers of mutations in BRCA2, a tumor suppressor gene product, have a higher risk of breast cancer. Canine BRCA2 has also been suggested to have a relationship with mammary tumors. However, clearly deleterious BRCA2 mutations have not been identified in any canine mammary tumors, and effects of BRCA2 mutations on tumorigenicity and genomic instability in dogs are unknown.
    In this study, 1. a PCR analysis method for canine BRCA2 was established, 2. effects of the missense mutations in canine BRCA2 on BRC repeats were elucidated, 3. tumour suppressor function of canine REIC/Dkk-3 in mammary gland tumors was analyzed.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, Competitive research funding, 23580399
  • Biological function and gene regulation of epididymal-specific carboxylesterase (CES4)
    Grants-in-Aid for Scientific Research
    2010 - 2012
    YAMASHITA Tetsuro; MORIMATSU Masami
    The biological function of an epididymal-specific carboxylesterase, CES4, was studied using Ces4 knock out mouse. The metabolome analysis of epididymal cell extracts revealed that the most of the glutathione was identified as oxidative form in the epididymis of KO mouse. The expression of oxidative stress-responsive heme oxygenase-1 (HO-1) was also increased in the KO mouse tissue. These data indicated that the epididymis of KO mouse was exposed by oxidative stress.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Iwate University, 22580100
  • Regulation Mechanisms of the body size in mice
    Grants-in-Aid for Scientific Research
    2009 - 2011
    KANO Kiyoshi; MORIMATSU Masami
    We analyzed phenotypes of DDR2 transgenic mice and ATDC5 cell lines with a focus on growth and size control. In previous study, cartilage cell proliferation decreased in DDR2 KO mice, and we analyzed also the function of DDR2 in cartilage tissue. We produced Ddr2 cDNA transgenic mice, which were specifically overexpressed only in the cartilage cells, but there were no prominent phenotypes in cartilage tissue of the transgenic mice.
    To understand the role of Ddr2 in chondrocyte proliferation and differentiation, we next performed knockdown experiments using Ddr2 miRNA in ATDC5 cells. We found that DDR2 might repress cell proliferation and differentiation in cartilage cells.
    DDR2 is suggested to have important function especially in the reproductive organs by the expression in various tissues.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), 21580344
  • Analysis of a novel NFkB inhibitor deficient mouse as a model for atopic dermatisis
    Grants-in-Aid for Scientific Research(基盤研究(B))
    2007 - 2009
    Masami MORIMATSU; Yukiko TOMIOKA; Katsuhiko OMOE; Kiyoshi KANO; Sadatoshi MAEDA
    MAIL (molecule possessing ankyrin-repeats induced by LPS) is a nuclear IkappaB protein that is also termed inhibitor of nuclear factor kappaB (IkappaB) zeta. We generated Mail-deficient mice that appeared to develop atopic dermatitis (AD). In this study, we tried to rescue embryonic lethality of the mice. We investigated expression and function of MAIL in the skin to elucidate its role in AD. Possible interactions of Mail with some genes were also investigated.
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Principal investigator, Competitive research funding, 19380164
  • Expression and role of sugar-recognition molecule galectin in the digestive tract
    Grants-in-Aid for Scientific Research
    2005 - 2006
    IWANAGA Toshihiko; MORIMATSU Masami
    Galectin is an animal lectin that recognizes β-galatosides of glycoconjugates and is abundant in the gut and urogenital tract. This study revealed the cellular expression of galectin subtypes in the digestive tract, kidney and ovary of mice by in situ hybridization and immunohistochemistry. Signals for five subtypes (galectin-2,-3,-4/6, and-7) were detected exclusively in the epithelia of digestive tract. In the glandular stomach, galectin-2 and-4/6 were predominantly expressed from the 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. In the large intestine, galectin-4/6 were 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. In the urinary system, the major subtype was galectin-3, which was expressed in the collecting ducts and transitional epithelium continuously from the kidney to the distal end of the urethra, suggesting selective expression of galectin-3 in epithelia of uretic bud and cloaca-derivatives. Galectin-1 and-3 were predominant in the ovary. The corpus luteum at particular stages of regression intensely expressed both types of galectins. Galectin-3 was restricted to regressing corpus luteum and always coincident to the expression of a progesterone degradation enzyme. The signal intensity of galectin-1 first increased at the starting point of regression followed by increasing expression of galectin-3. This finding suggest that galectin-1 and-3 may mediate the progesterone production and metabolism in luteal cells via different mechanisms. Because multi-functions of galectins, information on their cell/stage-specific expression contributes to a better understanding of the functions and pathological involvements of galectins.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 17390048
  • 新規アトピー性皮膚炎原因遺伝子の機能解析
    科学研究費補助金(萌芽研究)
    2005 - 2006
    森松 正美
    研究代表者らは炎症刺激で誘導される遺伝子をスクリーニングする過程で機能未知の遺伝子を同定し、MAILと命名した。ジーンターゲティングによりこの遺伝子を破壊したマウスを作製したところ、ホモ型欠損マウスの顔面を中心にアトピー性皮膚炎様の病変が認められた。本研究の第1の目的は、申請者が開発したMAIL破壊マウスを用いてMAILの機能を解析するとともに、これを疾患モデル動物として確立することである。第2の目的は、このモデルマウスの原因遺伝子が、ヒトでもアトピー性皮膚炎と関係があるか否かを探ることである。1.マウスの交配と維持:MAILのホモ欠損型が胎生期致死となることが原因でマウスの数が不足している点が研究を進める上で支障となっていた。交配規模を拡大し,産子の遺伝型をPCRにより判定して欠損マウスを得た。2.マウスの病態解析:MAILがケラチノサイトの初代培養や株化細胞で無刺激の状態でも発現していることを明らかにした。この発現には転写因子NF-kappaBが重要な役割を果たすことがわかった。この発現は,炎症性サイトカインによって上昇することが判明し,MAILが皮膚炎病態に関わっていることが示唆された。さらに皮膚炎を発症しているMAIL破壊マウスの皮膚組織を検索したところ,アトピー性皮膚炎に関与すると考えられているTh2系サイトカインの産生が認められた。3.ヒトの遺伝子解析:ヒトの皮膚生検試料におけるMAILの発現をin situ hybridizationで検索したが,はっきりした発現は認められなかった。今後,検出感度を上昇させるなどの方法の改善が望まれる。さらに,ヒトMAIL遺伝子の多型と皮膚炎との関係を調べるために,MAILのcDNAをRT-PCRで増幅するためのプライマーを設計し,疫学的解析を実施するための基盤を築いた。
    文部科学省, 萌芽研究, 北海道大学, Principal investigator, Competitive research funding, 17659109
  • Molecular and clinical analysis for metastasis and invasion of cancers in small animals
    Grants-in-Aid for Scientific Research
    2003 - 2006
    SASAKI Nobuo; TSUJIMOTO Hajime; NISHIMURA Ryohei; NAKAYAMA Hiroyuki; MORIMATSU Masami; MOCHIZUKI Manabu
    In this study, we tried to analyze the mechanism of tumor metastasis and local invasion in small animals using 5 cell lines established in our laboratory.
    In canine mammary cancer, expression and function of E-cadherin and catenin were compared between 4 pairs of cell lines established from the primary or metastatic lesions of the same patients. As a result, there were no differences in their expression but their function was higher in cell lines established from the metastatic lesions than those from primary lesions. This may indicate that the cells in the metastasis with low E-cadherin function are easily released from the primary lesions. In addition, sLe(x), an adhesion molecule to the endothelial cells, was alos highly expressed in one of the cell lines established from the thoracic effusion due to metastasis. Our previous data showed sLe(x) was 60% positive in the mammary tumor tissues, but not in normal mammary gland. From these data, sLe(x) may play a role in the metastasis of canine mammary tumors. Currently one of this mammary tumor cells was cloned and microarray analysis was conducted to clarify the genetic change in the cells from primary and metastatic lesions in nude mice model. The result may suggest some important molecules including NfκB and hipoxia related one, which will be analyzed in the future.
    In feline mammary tumors, we established 8 cell lines including 2 pairs from primary and metastatic lesions of the same patient. Using these cell lines, expression of a chemokine receptor CXCR4 and its ligand SDF-1 were compared between cell lines. Their expression was higher in those originated from metastasis than primary lesions, suggesting they may also play a role in tumor metastasis in feline mammary tumors. In addition, tumor-suppressing molecule, Braca2, was also analyzed in relation to the malignancy of this tumor.
    Retinoids, vitamin A derivatives, may control the growth of canine mast cell tumors. This tumor growth-inhibitory effect of retinoids against canine mast cell tumors was mediated by a receptor RAR alpha and via inducing apoptosis in both in vitro model and in vivo nude mice model, as in human acute promyelocytic leukemia. These results suggest the retinoids may be a potential chemotherapeutic agent for canine mast cell tumors. For canine osteosarcoma, gene therapy using wild type p53 transfection using adenovirus as a vector virus. This trial showed some efficacy in nude mice model and even in the canine patients with ostesarcoma. For canine melanoma, spindle check point function is currently investigated to analyze its relationship to chemotherapeutic response of the tumor.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), The University of Tokyo, 15208030
  • ウシ肝cDNAマイクロアレイの評価と妊娠ウシ肝の特異発現遺伝子の検索
    科学研究費助成事業
    2004 - 2005
    橋爪 一善; 木崎 景一郎; 高坂 哲也; 森松 正美
    ウシ肝臓由来cDNAクローンを基に作製したウシ肝cDNAマイクロアレイの有効性を未知クローンの配列、機能、発現動態の解析、検証することから、ウシ肝の生理状態の把握および疾病診断に適用できる汎用的なアレイの開発を目的として、より広範な遺伝子情報を集積した約10,000オリゴ情報からなるアレイを作製した。
    発現遺伝子動態の解析には体細胞クローンウシと通常の方法で作出したウシ肝臓を用いた。体細胞クローンウシでは病理および組織学的に変異を示す肝臓が認められるが、著しい病理変異を示さない肝臓であっても数%の遺伝子の発現変動を認め、cDNAアレイに含む数多くの遺伝子情報は、現在のところ機能が十分明確でなくとも肝臓の機能診断に有効な情報であることが示唆された。また、機能および遺伝子の全配列が不明であったcDNAクローンからその発現動態およびin silico解析により、2種の新規遺伝子であるプロラクチン関連タンパク質(PRP)遺伝子を同定し、PRP-VIIIおよび-IXと命名するとともに、in situ hybridizationにより主たる発現細胞が胎盤の二核細胞であることを証明した。加えて、これまで開発してきたウシ肝cDNAマイクロアレイおよび子宮・胎盤cDNAマイクロアレイ上の共通する遺伝子の検証およびin silico解析することから、約10,000オリゴを配置したウシオリゴアレイを作製した。このオリゴアレイは約2,620個の肝由来クローン情報および約1,730個の子宮・胎盤由来クローンを軸として、Gene Bank Database情報を基に抽出した約5,600遺伝子の60塩基配列からなる個別遺伝子情報を集積したものである。尚、本アレイの作製は、これまでアレイ開発で連携してきた農業生物資源研究所のグループとの共同成果である。
    日本学術振興会, 萌芽研究, 岩手大学, 16658105
  • Regulation of host defense and development by innate-immunity signal transduction system
    Grants-in-Aid for Scientific Research(基盤研究(B))
    2003 - 2005
    Masami MORIMATSU; Kumiko YOSHIMATSU; Yoshio YAMAMOTO
    In innate immune system, specific pattern molecules such as LPS bind to Toll-like receptors and activate signal transduction pathway involving NF-kappaB. Recently we identified a novel nuclear IkB molecule, MAIL. In this study we focused on MAIL and other NF-kappaB related molecules.1. Analysis of MAIL deficient miceEmbryonic lethality was observed for about 90% of MAIL deficient mice. Hypoplasia of the liver was suggested to be a possible cause for this embryonic lethality. Remaining 10% of MAIL deficient mice were born alive. These mice developed severe atopic dermatitis-like disease.2. Analysis of transcriptional regulation of the MAIL geneWe cloned LPS-reactive upstream region of the mouse MAIL gene, and analyzed its promoter function by using a series of mutated sequences. An NF-kappaB binding site located at -229 to -220 bp was revealed to be an essential target of MAIL expression. Overexpression of MAIL protein suppressed the LPS-induced promoter activity of the MAIL gene. These data indicate that MAIL expression is upregulated by NF-kappaB, and it is controlled, at least in part, by an autoregulation mechanism.3. Analysis of an NF-kappaB target gene product, BRCA2BRCA2, an NF-kappaB target molecule, plays essential roles for cell growth and embryogenesis through its DNA repair and recombination function. We demonstrated that BRCA2 proteins from the mouse and dog interact with Rad51 recombinase. We found a novel insertion/deletion polymorphism in canine BRCA2, which is located in a nuclear localization signal. This polymorphism was associated with nuclear localization efficiency and mammary tumor morbidity.
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 岩手大学->北海道大学, Principal investigator, Competitive research funding, 15380201
  • ジーンターゲティングによる新規アトピー性皮膚炎モデル動物の開発
    科学研究費補助金(萌芽研究)
    2003 - 2004
    森松 正美
    最近、ある機能未知の遺伝子を同定して機能解析のためにジーンターゲティングによりこの遺伝子を破壊したマウスを作製したところ、ホモ型欠損マウス(仮にAllergic Dermatitis、ALDマウスと呼ぶ)の顔面を中心にアトピー性皮膚炎様の病変が認められた。本研究の目的は、外見的に皮膚炎を認めるALDマウスについてその病態を解析し、これを疾患モデル動物として確立することである。1.マウスの交配と維持:研究の途中で岩手大学から北海道大学に拠点を移したが、いずれの場所でも問題なく微生物学的に清浄な環境でマウスを飼育した。繁殖規模を拡大すると同時に近交系への戻し交配を進めた。また、万が一の事故に備えて受精卵を凍結保存させた。2.病態の解析:皮膚病変部位の組織学的検索を行い、白血球系細胞の細胞浸潤による炎症反応を認めた。皮膚病変部では、ケモカインであるTARCとeotaxin、ケモカイン受容体であるCCR3の増加が認められた。これらはヒトのアトピー性皮膚炎とよく似た所見であり、MAIL欠損マウスが良いモデルとなる可能性を示すものである。正常マウスでのMAILの発現を免疫組織化学およびリアルタイムPCRで検索したところ、表皮ケラチノサイトでの発現を認めた。この結果は、ケラチノサイトのMAILが皮膚の恒常性に重要であり、これが欠損すると皮膚炎を発症することを示唆している。マウスの系統によって免疫応答に差があることが報告されているので、Th1優勢のC57BL/6、およびTh2優勢のBALB/cへの戻し交配を進めたが、いずれの系統でもMAIL欠損マウスで皮膚炎が認められた。以上より、本遺伝子操作マウスを疾患モデル動物として応用するための基盤の整備を進めることができた。
    文部科学省, 萌芽研究, 岩手大学->北海道大学, Principal investigator, Competitive research funding, 15658086
  • Development of hantavirus vaccine and rapid diagnosis kit by using soluble recombinant envelope glycoproteins
    Grants-in-Aid for Scientific Research
    2001 - 2003
    MORIMATSU Kumiko; ONO Eriko; MORIMATSU Masami; KARIWA Hiroaki; ARIKAWA Jiro
    1. It was clarified that recombinant Hantavirus envelope glycoproteins G1 and G2 (GPs) had the cell-fusion activity by using CAG promotor-expression system. Fusion-responsible epitope on GPs was found to locate in the neutralization (FRNT)-relating epitope. Therefore, the recombinant GPs was considered to possess neutralization-and fusion-relating epitopes. In addition, hantavirus nucleocapsid (N) protein was also expressed in mammalian cells by using same vector. As the result the N protein may suppress that expression and transportation of the envelope protein. It was also shown that the virus like particle was not formed by GPs and N protein alone.
    2. By using recombinant GPs, pseudotype vesicular stomatitis virus (VSV) enveloped with hantavirus GPs altered to VSV G protein was produced (VSVΔG*HTN). Similar pseudotype VSV was produced with recombinant GPs of Seoul virus (VSVΔG*SEO). These pseudotypes were applied to rapid neutralization assay as safety alternatives of authentic viruses. These pseudotype virus particles were also applied to vaccination as alternatives to authentic virion. Mice were immunized with soluble recombinant GPs or pseudotype virion. In mice immunized with soluble recombinant GPs, FRNT antibody was not detected. Contrary, in mice immunized with VSVΔG*HTN virion, FRNT antibody was detected. Challenge administration of hantavirus was carried out by s.c. inoculation of 4 FFU of hantavirus. These mice did not show the elevation of anti-N antibody and hantavirus specific CD8 T cell response, indicating that the FRNT antibody could protect mice from hantavirus infection. On the other hand, all control mice immunized with VSVΔG*G or PBS could not escape from hantavirus infection. These results indicated that packaged recombinant GPs on VSV particle were possible to induce protective FRNT antibody. This study shows that novel approach for the development of vaccination of viruses that have difficulties in preparation of authentic virus particles.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 13556046
  • DNA repair defect, tumorigensis, and hereditary breast cancer gene Brca2 -Studies in vitro and in vivo, and association with Rad51.
    Grants-in-Aid for Scientific Research(基盤研究(B))
    1999 - 2001
    Masami MORIMATSU; 冨澤 伸行; Shuji TSUDA; Bunei SYUTO; Katsuhiko NISHIMORI; Nobuyuki TOMIZAWA
    To establish the bases of developing new methods for prevention, diagnosis, and therapy of breast cancer , we investigated in vitro and invivo functions of the Brca2 and other tumor associated genes. Especially, researches for the significance of the interaction of Brca2 and Rad51, application of Brca2 analysis in veterinary medicine, and roles IkB MAIL were carried out.1. Cloning and mutation analysis of canine Brca2Full length (about 10 kbp) of the cDNA for canine Brca2 was cloned and sequenced. For mutation analysis, DNA fragments were obtained by PCR and used for protein truncation tests.2. Cloning and expression of feline Brca2Full length (about 10 kbp) of the cDNA for feline Brca2 was cloned and sequenced. Expression of feline Brca2 was confirmed in mamnary gland.3. Interaction of Brca2 and Rad51Interaction of C-terminus of canine Brca2 with Rad51 was demonstrated by yeast two-hybrid assay. Transactivation activity of canine Brca2 was also demonstrated.4. Characterization of a novel IkB protein, MAILWe cloned, sequenced, and analyzed the expression of the MAIL gene encoding a novel IkB protein.
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 岩手大学, Principal investigator, Competitive research funding, 11460133
  • Study for the development of new gene targeting method utilizing epitope tags
    Grants-in-Aid for Scientific Research(基盤研究(B))
    1999 - 2001
    Masami MORIMATSU; Kumiko YOSHIMATSU; Kazushige OGAWA; Bunei SYUTO; 吉村 佳典; Ichiro MIYOSHI; Yoshimichi YOSHIMURA
    To establish the bases for developing new methods of gene targeting, we investigated the efficiency of gene knock-in and the use of specific markers called epitope-tags. By using this approach, gene of interest is to be analyzed by antibodies against epitope-tags. We selected some genes for targeting experiments. Detailed characterization of candidates for epitope-tags was also carried out.1. Investigation of a novel endotoxin-inducible gene, MAIL, as a target.MAIL is suitable for targeting experiment because it is known that transcription of the gene is markedly up-regulated by endotoxin stimulation and that the gene product is specifically localized in the nucleus. We cloned and sequenced the genomic DNA of MAIL. Targeted disruption of MAIL gene was also performed.2. Investigation of genes encoding chitinase as a target.Because of tissue-specificity of chitinase gene, we choose this gene as a target. We cloned, sequenced, and analyzed expression pattern of chitinase gene, and established the basis for gene targeting.3. Investigation of other target genes.Inducible genes, such as B-13, and tissue-specific genes, such as glucose transporters, were investigated as targets.4. Analysis of epitope-tags.Antigenic specificity and cellular function of candidate epitope-tags from hantavirus proteins were examined.5. Developing knock-in method.We tried two-step targeting method for gene knock-in. However, expected recombinants were not obtained.Further research is needed to clarify the cause of the failure.
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 岩手大学, Principal investigator, Competitive research funding, 11556064
  • Fundamental studies on the protective mechanisms of a novel serum lectin (CBPb01)
    Grants-in-Aid for Scientific Research
    1999 - 2000
    SYUTO Bunei; MORIMATSU Masami
    The activation of the neutorophil function, such as phagocytosis and superoxide production induced by opsonins, is a very important system in the nonspecific defense, and its mechanism has been studied extensively. On the other hand, we have hypothesized that some kinds of regulatory proteins to the neutrophil activation system are present in serum and play the important roles as a regulatory systems. This hypothesis motivates us to isolate and to characterize a regulatory protein in the bovine serum. In this study, a bovine serum protein which binds to chitin (chitin binding protein, BPb01) and suppresses the superoxide generation in neutorphils has been purified and identified. The outline of the studies is as follows.
    1) A protein with high affinity to N-acetyl-D-glucosamine (GlcNAc) was separated and was named CBPb01.
    2) Purification and identification : the amino acid sequence of CBPb01 peptides were identical to the reported amino acid sequence of bovine IgM.
    3) Constituent carbohydrates : lectin binding analysis revealed that CBPb01 contains mannose, GlcNAc and fucose.
    4) Inhibition of superoxide generation by CBPb01 : about 40% of superoxide generation was decreased, when a neutrophils were stimulated with the opsonized zymosan that was treated with CBPb01. This decrease was completely inhibited by adding GlcNAc.
    We have concluded that CBPb01 is not a lectin but a GlcNAc recognizing IgM that regulate the superoxide generation in neutrophils.
    5) Inhibition mechanism for the superoxide generation by CBPb01 : although CBPb01 binds to neutrophils, the superoxide generation was not decreased. These results suggest that CBPbO1 inhibits the active structure of protein complex formed with opsonins, while it does not involve the process of the down stream from phospholipase C to NADPH oxidase activation in the superoxide generation system.
    6) This is the first report of the chitin-binding bovine IgM that controls a superoxide generation in neutrophils.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Iwate University, 11660292
  • 近赤外光を用いたイヌの脳活動の無侵襲計測 - イヌのこころの動きを測る
    科学研究費補助金(萌芽的研究)
    1999 - 1999
    森松 正美; 冨澤 伸行
    脳の多彩な精神活動は,神経細胞によるエネルギー代謝とそれにともなう酸素の消費によって支えられている.脳活動が変動すると脳の血流量や血液内ヘモグロビン(Hb)の酸素化度が変化するため,これらを測定することは,動物の精神活動を探る糸口となることが期待される.本研究ではイヌの精神活動の分析に,近赤外分光法による脳Hb酸素化度の測定が利用可能か否かを検討した.1.麻酔下のイヌによる脳血流測定の基礎的解析脳血流量を測定する際に筋血流量の影響が障害となる可能性があるため,麻酔下のイヌを用いて検討した.プローブを外科的処置により露出させた頭蓋骨表面に装着した場合と,皮膚表面からあてた場合とで測定値を比較し,測定における筋血流量の影響を調べた.呼気中酸素分圧や頚動脈の開閉等を行って検討した.プローブを頭部正中に装着すれば,筋血流量の変化の影響を抑えて脳血流量を測定できる可能性が高いことが示された.さらに,脳特異的血流変化が検出できるかどうかを検討した.脳は二酸化炭素に感受性が高いため,これを吸入させてその影響を調べたところ,脳に特徴的な変化が観察された.2.無侵襲・無麻酔・無拘束のイヌにおける脳血流測定イヌの情動変化を近赤外分光法で捉えることができるか否かを検討するため,イヌにとって望まれる状況と望まれない状況を設定し脳血流の変化を観察した.餌を与えて喜ばせた場合,Hb酸素化度の低下が認められた.別離不安の見られるイヌについて,飼い主がイヌから離れて隠れたところ,Hb酸素化度の一過性の上昇とそれに続く比較的長時間の低下が観察された
    文部科学省, 萌芽的研究, 岩手大学, Principal investigator, Competitive research funding, 11876056
  • 急性相タンパク質の新規動物資源生産管理および野生動物生態調査への応用
    科学研究費補助金(奨励研究(A))
    1997 - 1998
    森松 正美
    生体が、感染、炎症、ストレス等による侵襲を受けると、肝臓から血液中に特定の一群の生体防御関連タンパク質、すなわち急性相タンパク質が分泌される。この研究の目的は、急性相タンパク質の測定による動物の健康管理を新規家畜や野生動物に応用することにより、基礎研究及び関連産業の発展への貢献をはかることである。本研究では、クマおよびシカの急性相タンパク質に焦点をあてて、免疫測定法を確立するとともに飼育個体や野生個体における変動を解析して,これらの新規家畜や野生動物の健康管浬に利用することを計画した。平成10年度は,急性相タンパク質測定法の確立,試料の収集と測定の実施を中心に以下のごとく検討した.クマの急性相タンパク質:クマの急性相タンパク質のうち,ハプトグロビン(Hp),α2-マクログロブリン(α2M),α1-アンチトリプシン(α1-AT)およびC-反応性タンパク質(CRP)について単純放射免疫拡散法(SRID法)あるいはウエスタンプロット法による測定を行った。野生個体の捕獲例では,外見的に正常な個体に比べ外傷を負った個体で顕著なハブトグロビンの増加が認められた。健康な飼育個体で冬眠との関係に着目して調べたところ,冬眠に伴ってHpとα2Mが増加したが,α1-ATとCRPは変化しなかった。クマの健康管理に急性相タンパク質の測定が有用であると思われるが,冬眠など生理的な変化の影響について留意する必要がある。シカの急性相タンパク質:シカの血清をポリアクリルアミドゲル電気泳動により分析したところ,健康状態によって顕著に変化するタンパク質を見いだした。これを分離して分析し,シカHpと同定した。クマの例と同様に特異的な免疫測定法を確立して調べた結果,シカでHpが炎症性の刺激により急激に増加する良いマーカーとなりうろことが示された。
    文部科学省, 奨励研究(A), 北海道大学->岩手大学, Principal investigator, Competitive research funding, 09760297
  • Neuroendocrine mechanism of stress-induced immunosuppression and roles of cytokines.
    Grants-in-Aid for Scientific Research
    1995 - 1996
    SAITO Masayuki
    Various types of stressor suppress immune activities. Previously, we have confirmed a significant role of the sympathetic nervous system (SNS) in the stress-induced immunosuppression. In this study, we examined the effects of brain stimulation on the sympathetically mediated immunosuppression in rats. When the ventromedial hypothalamus (VMH), a putative hypothlamic center linked to the SNS,was stimulated electrically, the proliferative activity of splenic lymphocytes was reduced. The suppressive effect of VMH was not affected by adrenalectomy, but abolished by ganglionic blockade and surgical sympathetic denervation. These results suggest a critical role of the VMH in the stress-induced immunosuppression. Similar suppressive effects were also observed when interleukin-1 (IL-1), a representative cytokine produced in immune cells and brain cells, was given intracerebroventricularly. Brain IL-1 was also found to accelerate noradrenaline turnover in various peripheral organs, implying increased activity of the SNS.There are reports that the stress-induced immunosuppression was attenuated by intracranial injection of anti-IL-1 antibody. Collectively, it was concluded that brain IL-1 and the VMH play important roles in the stress-induced immunosuppression.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 07456128
  • ウシ肝細胞における急性相タンパク質の遺伝子発現調節機構の解析
    科学研究費補助金(奨励研究(A))
    1995 - 1995
    森松 正美
    急性相タンパク質は、炎症性サイトカインが肝細胞を刺激することにより合成・分泌される血清タンパク質の総称であり、生体の防御・免疫機能に関与している。申請者はこれまでウシの急性相タンパク質の血中レベルの変動等について研究を進め、ラット等の実験動物やヒトでこれまで報告されてきたものとは異なるいくつかの特徴的な現象を見いだしてきた。本研究ではこれを更に発展させ,この現象の根幹となる遺伝子発現調節機構をin vitroの肝細胞培養実験系を用いて解明することを試み,いくつかの新知見を得ることができた。[1]ウシ急性相タンパク質の型別(I型とII型)の検討近年、ラットやヒト由来の材料を用いた研究結果に基づき、急性相タンパク質は作用するサイトカインの種類によりI型(インターロイキン(IL)-1と腫瘍壊死因子(TNF)が例外無くともに作用し,IL-6も効果があることがある)とII型(IL-6でのみ誘導される)に分類されるのが一般的となってきた。申請者は,これがウシの急性相タンパク質にもあてはまるか否かを明らかにするため,ウシのハプトグロビン(Hp),C-反応性タンパク質(CRP),alpha 1-酸性糖タンパク質(al-AG),alpha 2-マクログロブリン(a2-MG)のcDNAをそれぞれクローニングしてこれをプローブとし,サイトカインで刺激したウシの初代培養肝細胞におけるこれら急性相タンパク質のmRNA発現量をNorthernハイブリダイゼーション法で解析した。その結果,ラットやヒトでI型急性相タンパク質と考えられているHp,CRP,al-AGがいずれもTNFとIL-6で誘導されるがIL-1では誘導されないことを明らかにした.すなわち,これまでラットやヒトで提唱されているI型とII型の分類はウシにあてはまらないことを発見し,ウシに特有の急性相タンパク質合成調節機構が存在することが示唆された。[2]ウシ特有の上記機構解明の試み上記(1)についてHp,CRP,al-AGがラットやヒトでI型であることを考えると、ウシでもこれらが基本的にはI型類似だが、何らかの因子の欠陥によりIL-1に不応答であると予想できる。このウシ肝細胞に欠けている因子を遺伝子相補により単離することを最終目標としてそれに不可欠なウシ肝細胞株の樹立を試みた。ウシ初代培養肝細胞にSV40ウイルス由来の大型T抗原(LT)を導入して不死化することを試みた。哺乳動物細胞発現ベクターあるいはアデノウイルスに組み換えたLTを導入したところ,長期培養に耐える細胞がいくつか得られたが,残念ながらこれらでは急性相タンパク質遺伝子の発現を認めなかった。現在,不死化の方法を変更してさらにウシ肝細胞株樹立を試みている。
    文部科学省, 奨励研究(A), 北海道大学, Principal investigator, Competitive research funding, 07760270
  • ウシハプトグロビン遺伝子の構造および転写調節機構の解析
    科学研究費補助金(奨励研究(A))
    1994 - 1994
    森松 正美
    ハプトグロビン(Hp)は,肝臓で合成・分泌される血清タンパク質であり,急性炎症時に血中レベルが上昇して生体の防御・免疫機能に関与する急性相タンパク質のひとつである.本研究では,ウシHpに着目し,その遺伝子進化の背景をさぐるとともに,特徴的な遺伝子転写調節機構について,いくつかの新知見を得ることに成功した.1.ウシHp遺伝子の進化申請者はこれまでの研究成果から,ウシのHpは特徴的な遺伝子重複による分子進化を経て形成されたと予想した.本研究では,ウシゲノムDNAをサザンブロット法で解析して制限酵素地図を作製したところ,ゲノム上に単一コピーで存在することが明らかとなり,重複前の遺伝子は著しく変異したか,あるいはすでに欠失したと予想した.さらに,他の哺乳動物のHpをタンパク質レベルで調べた結果から,ウシで発見した遺伝子重複による分子進化は,広く反芻動物に認められることを明らかにした.なお,当初の実験計画では,ウシHpのゲノムDNAをクローニングして全塩基配列を決定する計画であったが,残念ながらまだクローニングには成功しておらずこの実験は継続中である.2.ウシHp遺伝子の転写調節ウシ肝臓におけるmRNA量を調べたところ,Hpの発現は,正常では極めて低いが炎症性疾患で急激に上昇することを明らかにした.さらに,ウシ初代培養肝細胞実験系で調べたところ,炎症性サイトカインのうち,インターロイキン(IL)-6と腫瘍壊死因子(TNF)が,Hp遺伝子の転写を誘導したが,IL-1は効果がなかった.このことは,これまでに報告された急性相タンパク質では,TNFで誘導されるものは例外なくIL-1でも誘導され,両者が共通の細胞内情報伝達系を活性化するとされてきたことと極めて対照的な新知見である.また,泌乳ホルモンであるプロラクチンがウシHpの遺伝子発現を誘導することを,あらゆる急性相タンパク質の中で初めて発見した.
    文部科学省, 奨励研究(A), 北海道大学, Principal investigator, Competitive research funding, 06760249
  • Molecular mechanisms of the central actions of interleukin-1
    Grants-in-Aid for Scientific Research
    1993 - 1994
    SAITO Masayuki; MORIMATSU Masami
    It has been established that the central nervous system and the peripheral immune system interact in a biderectional manner. Interleukin-1 (IL-1) is one of the cytokines for the communication between these two systems. In this study, to clarify the cellular and molecular mechanisms for the central action of IL-1, we examined the effects of IL-1 on norepinephrine (NE) turnover (an index of noradrenergic neuronal activity) in the brain and peripheral organs in rats, and obtained the following results :
    1. When IL-1 was given intraperitoneally, it increased NE turnover in the hypothalamus and also in some peripheral organs such as spleen and lung. These responses were mimicked by an intracerebroventricular (icv) injection of minute amounts of IL-1, suggesting a direct action of IL-1 to the brain.
    2. The stimulative effects of IL-1 were completely blocked by the pretreatment with either an antibody against corticotropin-releasing hormone (CRH) or indomethacin, an inhibitor of prostaglandin (PG) biosynthesis, suggesting important roles of brain CRH and PGs for the IL-1 action.
    3. An icv injection of CRH could activate NE turnover in every organs in the same way as the IL-1 injection. In contrast, PGs given intracerebroventricularly were effective for NE turnover in some limited organs : that is , PGE2 for spleen and lung, and PGD2 only for the hypothalamus. Thus, the signal of IL-1 may be converted to the production of PGD2 and PGE2 to activate the noradrenergic neurons projecting to the hypothalamus and peripheral organs, respectively. The molecular mechanisms for such differential regulation of PG production in the brain remain to be further investigated.
    Japan Society for the Promotion of Science, Grant-in-Aid for General Scientific Research (B), Hokkaido University, 05454116
  • ウシの初代培養肝細胞を用いた急性相タンパク質の遺伝子発現・合成調節機構の解析
    科学研究費補助金(奨励研究(A))
    1993 - 1993
    森松 正美
    急性相タンパク質は、主に肝臓により合成・分泌され、急性炎症時に特徴的な血中動態を示しながら生体の防御・免疫機能に関与している。本研究では、ウシ肝細胞の初代培養系を確立して急性相タンパク質の合成調節機構を細胞・分子レベルで解明するための基礎を築くとともにいくつかの新知見を得ることに成功した。1.ウシ肝細胞の初代培養の確立(1)ウシから肝尾状葉を摘出後、コラゲナーゼを灌流して結合組織を消化し、肝細胞を分離する方法を確立した。肝摘出前にヘパリンをウシに注射して血液凝固を抑制することにより実験の再現性が向上した。また、灌流するコラゲナーゼの濃度は0.05%が、灌流時間は10〜15分間が適当であった。(2)分離した肝細胞を培養することにより、タンパク質合成とグリコゲン分解の活性が上昇した。培養条件はラットのものを応用したが、ラットの場合と同様に、肝特異的代謝活性は培養開始後一週間で再び低下した。2.初代培養肝細胞を用いた急性相タンパク質の合成調節機構の解析(1)まず、ウシの急性炎症で血中に最も急激に上昇するハプトグロビン(Hp)について調べた。肝細胞の培養上清に放出されたHpを特異抗体で免疫沈降して測定した。調べた炎症性サイトカインのうち、インターロイキン6(IL-6)と腫瘍壊死因子(TNF)はHpの合成を誘導したが、IL-1では変化がなかった。特に、TNFが誘導する点は、ラット等とは異なる点であり、in vivoにおける急激な上昇と関係があるものと推察できる。(2)急性炎症のみならず泌乳に関連して変動するC-反応性タンパク質(CRP)について、上記Hpと同様に免疫沈降実験を行った。しかし、現在までのところCRPの検出に成功していない。これについては、検出感度を上昇させるべく特異抗体の再調製を行うとともに、遺伝子発現レベルでの変化の解析を行っているところである。
    文部科学省, 奨励研究(A), 北海道大学, Principal investigator, Competitive research funding, 05760216
  • 炎症反応の制御に関わる細胞情報伝達機構
    Competitive research funding
  • 相同組換え反応の分子機構
    Competitive research funding
  • 家畜の急性相タンパク質の合成・分泌調節機構
    Competitive research funding
  • Signal transduction mechanisms in the inflammatory response
    Competitive research funding
  • Molecular mechanisms of homologous recombination.
    Competitive research funding
  • Mechanisms of the synthesis and secretion of acute-phase proteins in domestic animals.
    Competitive research funding
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    10 Jul. 2018 - Present
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    01 Sep. 2017 - Present
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