研究者データベース

安居院 高志(アグイ タカシ)
獣医学研究院 獣医学部門 応用獣医科学分野
教授

基本情報

所属

  • 獣医学研究院 獣医学部門 応用獣医科学分野

職名

  • 教授

学位

  • 獣医学修士(北海道大学)
  • 獣医学博士(北海道大学)

J-Global ID

研究キーワード

  • 遺伝学   実験動物学   Laboratory Animal Science   

研究分野

  • ライフサイエンス / 実験動物学
  • ライフサイエンス / 獣医学
  • ライフサイエンス / 獣医学
  • ライフサイエンス / 獣医学

職歴

  • 2017年04月 - 現在 北海道大学大学院獣医学研究院 応用獣医科学分野 実験動物学教室 教授
  • 2002年 - 2017年03月 - 北海道大学大学院獣医学研究科動物疾病制御学講座実験動物学教室 教授
  • 1997年 - 2002年 名古屋市立大学医学部実験動物研究教育センター 助教授
  • 1997年 - 2002年 Associate Professor,Center for Laboratory Animal Science, Nagoya City University
  • 2002年 - Professor
  • 1992年 - 1997年 名古屋市立大学医学部動物実験施設 助教授
  • 1992年 - 1997年 Associate Professor,Institute for Animal Experimentation, Nagoya City University
  • 1989年 - 1992年 徳島大学医学部附属動物実験施設 助手
  • 1989年 - 1992年 Research Associate,Institute for Animal Experimentation, University of Tokushima School of Medicine
  • 1988年 - 1989年 National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S.A Visiting Associate
  • 1988年 - 1989年 Visiting Associate,National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S.A
  • 1987年 - 1988年 National Institute of Neurological and Communicative Disorders, National Institutes of Health, U.S.A Visiting Associate
  • 1987年 - 1988年 Visiting Associate,National Institute of Neurological and Communicative Disorders, National Institutes of Health, U.S.A
  • 1984年 - 1987年 National Institute of Neurological and Communicative Disorders, National Institutes of Health, U.S.A Visiting Fellow
  • 1984年 - 1987年 Visiting Fellow,National Institute of Neurological and Communicative Disorders, National Institutes of Health, U.S.A
  • 1984年 日本学術振興会 奨励研究員
  • 1984年 Post-Doctoral Fellow,Apr. 1984 - Sep. 1984 Postdoctoral Fellow, Japan Society for the Promotion of Science, Department of Biochemistry, Faculty of Veterinary Medicine, Hokkaido University

学歴

  •         - 1984年   北海道大学   獣医学研究科
  •         - 1984年   北海道大学
  •         - 1981年   北海道大学   獣医学研究科
  •         - 1981年   北海道大学
  •         - 1979年   北海道大学   獣医学部
  •         - 1979年   北海道大学

所属学協会

  • 日本動物実験代替法学会   日本実験動物医学会   日本実験動物学会   日本獣医学会   The Japanese Society of Veterinary Science   Japanese Society for Alternative to Animal Experiments   Japanese Association for Laboratory Animal Science   Japanese Association of Laboratory Animal ScienceJapanese Association of Laboratory Animal MedicineThe Japanese Society of Veterinary ScienceJapanese Society of Animal Models for Human Diseases   

研究活動情報

書籍

  • 現代実験動物学
    朝倉書店 2009年
  • 免疫実験法ハンド ブック
    名古屋大学出版会 2006年
  • 基礎生化学実験法 第2卷 生体試料
    東京化学同人 2000年
  • 最新実験動物学
    朝倉書店 1998年
  • 疾患別]モデル動物の作製と 新薬開発のための試験・実験法
    技術情報協会 1993年
  • Genetic Hypertension
    John Libbey Eurotext 1992年
  • The LEC Rat: A New Model for Hepatitis and Liver Cancer
    Springer-Verlag 1991年

その他活動・業績

  • Daisuke Torigoe, Atsushi Asano, Hideto Yamauchi, Dang Ruiha, Nobuya Sasaki, Takashi Agui JAPANESE JOURNAL OF VETERINARY RESEARCH 57 (4) 175 -184 2010年02月 [査読無し][通常論文]
     
    The hooded phenotype is one of the coat color phenotype seen peculiarly in the rat. The hooded locus showing autosomal recessive inheritance is mapped to chromosome (Chr) 14 and that the hooded phenotype receives modification by hooded-modifier gene showing the linkage to the hooded locus. However, a gene responsible for either the hooded or hooded-modifier gene is not yet identified. To clarify genetic control of hooded phenotype, we carried out genetic linkage studies using BN and LEA rats. For determination of phenotypic variation, we measured ratio of pigmented coat area in parental and their F, and F, rats. We, then, conducted a genome-wide scan on 152 F, rats for linkage with ratio of pigmented coat area for the dorsal, ventral, and total regions. A major quantitative trait locus (QTL), D14Got40, showing highly significant linkage contributing 70-90% of the variance for hooded phenotype was detected on Chr 14, which may be correspondent to the hooded locus. In addition, another QTL, D17Rat2, showing highly significant linkage was also detected on Chr 17 in dorsal region phenotype as well as a QTL showing suggestive linkage on Chr15 in ventral region phenotype. We, further, investigated a genome-wide scan for epistatic interactions and detected significant interactions between D14Got40 and D20Mit1, and between D14Got40 and D17Rat2 in the dorsal region phenotype. These results suggest that a major QTL in Chr 14, which is possibly correspondent to the hooded locus, mainly regulates the hooded phenotype with some modifier loci, two of which show epistatic interactions with the hooded locus.
  • Daisuke Torigoe, Atsushi Asano, Hideto Yamauchi, Dang Ruiha, Nobuya Sasaki, Takashi Agui JAPANESE JOURNAL OF VETERINARY RESEARCH 57 (4) 175 -184 2010年02月 [査読無し][通常論文]
     
    The hooded phenotype is one of the coat color phenotype seen peculiarly in the rat. The hooded locus showing autosomal recessive inheritance is mapped to chromosome (Chr) 14 and that the hooded phenotype receives modification by hooded-modifier gene showing the linkage to the hooded locus. However, a gene responsible for either the hooded or hooded-modifier gene is not yet identified. To clarify genetic control of hooded phenotype, we carried out genetic linkage studies using BN and LEA rats. For determination of phenotypic variation, we measured ratio of pigmented coat area in parental and their F, and F, rats. We, then, conducted a genome-wide scan on 152 F, rats for linkage with ratio of pigmented coat area for the dorsal, ventral, and total regions. A major quantitative trait locus (QTL), D14Got40, showing highly significant linkage contributing 70-90% of the variance for hooded phenotype was detected on Chr 14, which may be correspondent to the hooded locus. In addition, another QTL, D17Rat2, showing highly significant linkage was also detected on Chr 17 in dorsal region phenotype as well as a QTL showing suggestive linkage on Chr15 in ventral region phenotype. We, further, investigated a genome-wide scan for epistatic interactions and detected significant interactions between D14Got40 and D20Mit1, and between D14Got40 and D17Rat2 in the dorsal region phenotype. These results suggest that a major QTL in Chr 14, which is possibly correspondent to the hooded locus, mainly regulates the hooded phenotype with some modifier loci, two of which show epistatic interactions with the hooded locus.
  • IWATA Ryohei, SASAKI Nobuya, AGUI Takashi Biomed. Res. 31 (1) 83 -87 2010年 [査読無し][通常論文]
  • NISHINO Tomohiro, SASAKI Nobuya, NAGASAKI Ken‐ichi, AHMAD Zulkifli, AGUI Takashi J. Vet. Med. Sci. 72 (10) 1313 -1318 2010年 [査読無し][通常論文]
  • Hypothyroid phenotype of the Tpst2 mutant mouse is dependent upon genetic background
    Biomed. Res. 31 83 -87 2010年 [査読無し][通常論文]
  • Biomed. Res. 31 (1) 83 -87 2010年 [査読無し][通常論文]
  • J. Vet. Med. Sci. 72 (10) 1313 -1318 2010年 [査読無し][通常論文]
  • Hypothyroid phenotype of the Tpst2 mutant mouse is dependent upon genetic background
    Biomed. Res. 31 83 -87 2010年 [査読無し][通常論文]
  • A. Y. Simon, K. Moritoh, D. Torigoe, A. Asano, N. Sasaki, T. Agui INFECTION GENETICS AND EVOLUTION 9 (6) 1253 -1259 2009年12月 [査読無し][通常論文]
     
    Experimental infection of mice with Sendai virus (SeV) is frequently used as a model of viral pathogenesis of human respiratory disease. To understand the differences in host response to SeV among mice strains, we carried out genetic mapping studies in DBA/2 (D2) (susceptible) and C57BL/6 (B6) (resistant) mice. F(1), F(2), and N(2) backcrossed mice were generated and examined for their disease resistance and susceptibility. For the determination of virulence, percentage body weight loss and survival time were used as phenotypes. We, then, carried out a genome wide scan on 108 backcrossed mice for linkage with percentage body weight loss as phenotype. A major quantitative trait locus (QTL) showing significant linkage was mapped to the distal portion of Chr4 (SeV1). In addition, two other QTLs showing suggestive statistical linkage were also detected on Chr 8 and 14. We, further, performed genome scan for interactions with least squares analysis of variance of all pairs of informative makers in backcrossed progenies. We identified a highly significant epistatic interaction between D3Mit182 and D14Mit10, then denoted as SeV2 and SeV3, respectively, and the latter was the same locus showing a suggestive level on Chr 14 in QTL analysis. Considered genotypes of these three loci, we could account for more than 90% of genetic effect on the differential response to SeV infection between B6 and D2 mice. These findings revealed a novel gene interactions controlling SeV resistance in mice and will enable the identification of resistance genes encoded within these loci. (C) 2009 Elsevier B,V. All rights reserved.
  • NAGASAKI Ken‐ichi, NAGASAKI Ken‐ichi, IKOMA Toshiyuki, KATSUDA Shin‐ichi, TONEGAWA Toru, TANAKA Junzo, OHYAMA Minami, HAYASHIDA Kosuke, NAKAMURA Teppei, SATO Hidetaka, ITO Shigeo, SASAKI Nobuya, AGUI Takashi J. Vet. Med. Sci., 71 (10) 1365 -1371 2009年 [査読無し][通常論文]
  • NAGASAKI Ken‐ichi, NAGASAKI Ken‐ichi, IKOMA Toshiyuki, KATSUDA Shin‐ichi, TONEGAWA Toru, TANAKA Junzo, NAKAMURA Teppei, SATO Hidetaka, ITO Shigeo, SASAKI Nobuya, AGUI Takashi J. Vet. Med. Sci., 71 (6) 729 -736 2009年 [査読無し][通常論文]
  • HOSODA Yayoi, SASAKI Nobuya, AGUI Takashi J. Vet. Med. Sci., 70 (10) 1043 -1049 2008年 [査読無し][通常論文]
  • Atsushi Asano, Kouta Tsubomatsu, Cha-Gyun Jung, Nobuya Sasaki, Takashi Agui MAMMALIAN GENOME 18 (11) 779 -786 2007年11月 [査読無し][通常論文]
     
    Bone marrow (BM)-derived T-cell progenitors differentiate into CD4 or CD8 single-positive (SP) cells in the thymus. We have previously reported that a single autosomal mutation, thid, causes a defect in the maturation of CD4 SP thymocytes and an abnormality of peripheral helper T cells in the LEC rat. In this study we attempted to identify a gene responsible for the thid mutation. We first performed genetic linkage analysis and mapped the thid locus between Myb and D1Rat392 on Chr 1. In this region we found an approximately 380-kb deletion from intron 3 of the Ptprk gene, which encodes a receptor-like protein tyrosine phosphatase type kappa (RPTP kappa) to intron 1 of the RGD1560849 predicted gene in the LEC rat genome. Reconstitution with syngenic BM cells transduced Ptprk but not the RGD1560849 predicted gene rescued development of CD4 SP cells in the LEC rat thymus. It is confirmed by this result that the Ptprk gene is responsible for the thid mutation in the LEC rat. Our results further suggest that RPTP kappa plays a critical role in the development of CD4 SP cells in the thymus.
  • Atsushi Asano, Kouta Tsubomatsu, Cha-Gyun Jung, Nobuya Sasaki, Takashi Agui MAMMALIAN GENOME 18 (11) 779 -786 2007年11月 [査読無し][通常論文]
     
    Bone marrow (BM)-derived T-cell progenitors differentiate into CD4 or CD8 single-positive (SP) cells in the thymus. We have previously reported that a single autosomal mutation, thid, causes a defect in the maturation of CD4 SP thymocytes and an abnormality of peripheral helper T cells in the LEC rat. In this study we attempted to identify a gene responsible for the thid mutation. We first performed genetic linkage analysis and mapped the thid locus between Myb and D1Rat392 on Chr 1. In this region we found an approximately 380-kb deletion from intron 3 of the Ptprk gene, which encodes a receptor-like protein tyrosine phosphatase type kappa (RPTP kappa) to intron 1 of the RGD1560849 predicted gene in the LEC rat genome. Reconstitution with syngenic BM cells transduced Ptprk but not the RGD1560849 predicted gene rescued development of CD4 SP cells in the LEC rat thymus. It is confirmed by this result that the Ptprk gene is responsible for the thid mutation in the LEC rat. Our results further suggest that RPTP kappa plays a critical role in the development of CD4 SP cells in the thymus.
  • Nobuya Sasaki, Yayoi Hosoda, Aogu Nagata, Ming Ding, Ji-Ming Cheng, Tomomi Miyamoto, Shinya Okano, Atsushi Asano, Ichiro Miyoshi, Takashi Agui MOLECULAR ENDOCRINOLOGY 21 (7) 1713 -1721 2007年07月 [査読無し][通常論文]
     
    The growth-retarded (grt) mouse has an autosomal recessive, fetal-onset, severe thyroid hypoplasia related to TSH hyporesponsiveness. Through genetic mapping and complementation experiments, we show that grt is a missense mutation of a highly conserved region of the tyrosylprotein sulfotransferase 2 (Tpst2) gene, encoding one of the two Tpst genes implicated in posttranslational tyrosine Osulfation. We present evidence that the grt mutation leads to a loss of TPST2 activity, and TPST2 isoform has a high degree of substrate preference for TSH receptor (TSHR). The expression of TPST2 can restore TSH-TSHR-mediated cAMP production in fibroblasts derived from grt mice. Therefore, we propose that the tyrosine sulfation of TSHR by TPST2 is crucial for TSH signaling and resultant thyroid gland function.
  • Nobuya Sasaki, Yayoi Hosoda, Aogu Nagata, Ming Ding, Ji-Ming Cheng, Tomomi Miyamoto, Shinya Okano, Atsushi Asano, Ichiro Miyoshi, Takashi Agui MOLECULAR ENDOCRINOLOGY 21 (7) 1713 -1721 2007年07月 [査読無し][通常論文]
     
    The growth-retarded (grt) mouse has an autosomal recessive, fetal-onset, severe thyroid hypoplasia related to TSH hyporesponsiveness. Through genetic mapping and complementation experiments, we show that grt is a missense mutation of a highly conserved region of the tyrosylprotein sulfotransferase 2 (Tpst2) gene, encoding one of the two Tpst genes implicated in posttranslational tyrosine Osulfation. We present evidence that the grt mutation leads to a loss of TPST2 activity, and TPST2 isoform has a high degree of substrate preference for TSH receptor (TSHR). The expression of TPST2 can restore TSH-TSHR-mediated cAMP production in fibroblasts derived from grt mice. Therefore, we propose that the tyrosine sulfation of TSHR by TPST2 is crucial for TSH signaling and resultant thyroid gland function.
  • Shekar Menon, Jaemin Lee, William A. Abplanalp, Sung-Eun Yoo, Takashi Agui, Sen-ichi Furudate, Paul S. Kim, Peter Arvan JOURNAL OF BIOLOGICAL CHEMISTRY 282 (9) 6183 -6191 2007年03月 [査読無し][通常論文]
     
    Newly synthesized thyroglobulin (Tg), the secretory glycoprotein that serves as precursor in thyroid hormone synthesis, normally forms transient covalent protein complexes with oxidoreductases of the endoplasmic reticulum (ER). The Tg-G2320R mutation is responsible for congenital hypothyroidism in rdw/rdw rats, in which a lack of secondary thyroid enlargement (goiter) implicates death of thyrocytes as part of disease pathogenesis. We found that mutant Tg-G2320R was retained within the ER with no detectable synthesis of thyroxine, had persistent exposure of free cysteine thiols, and was associated with activated ER stress response but incomplete ER-associated degradation (ERAD). Tg-G2320R associated with multiple ER resident proteins, most notably ERp72, including covalent Tg-ERp72 interactions. In PC C13 thyrocytes, inducible overexpression of ERp72 increased the ability of cells to maintain Tg cysteines in a reduced state. Noncovalent interactions of several ER chaperones with newly synthesized Tg-G2320R diminished over time in parallel with ERAD of the mutant protein, yet a small ERAD-resistant Tg fraction remained engaged in covalent association with ERp72 even 2 days post-synthesis. Such covalent protein aggregates may set the stage for apoptotic thyrocyte cell death, preventing thyroid goiter formation in rdw/rdw rats.
  • Shekar Menon, Jaemin Lee, William A. Abplanalp, Sung-Eun Yoo, Takashi Agui, Sen-ichi Furudate, Paul S. Kim, Peter Arvan JOURNAL OF BIOLOGICAL CHEMISTRY 282 (9) 6183 -6191 2007年03月 [査読無し][通常論文]
     
    Newly synthesized thyroglobulin (Tg), the secretory glycoprotein that serves as precursor in thyroid hormone synthesis, normally forms transient covalent protein complexes with oxidoreductases of the endoplasmic reticulum (ER). The Tg-G2320R mutation is responsible for congenital hypothyroidism in rdw/rdw rats, in which a lack of secondary thyroid enlargement (goiter) implicates death of thyrocytes as part of disease pathogenesis. We found that mutant Tg-G2320R was retained within the ER with no detectable synthesis of thyroxine, had persistent exposure of free cysteine thiols, and was associated with activated ER stress response but incomplete ER-associated degradation (ERAD). Tg-G2320R associated with multiple ER resident proteins, most notably ERp72, including covalent Tg-ERp72 interactions. In PC C13 thyrocytes, inducible overexpression of ERp72 increased the ability of cells to maintain Tg cysteines in a reduced state. Noncovalent interactions of several ER chaperones with newly synthesized Tg-G2320R diminished over time in parallel with ERAD of the mutant protein, yet a small ERAD-resistant Tg fraction remained engaged in covalent association with ERp72 even 2 days post-synthesis. Such covalent protein aggregates may set the stage for apoptotic thyrocyte cell death, preventing thyroid goiter formation in rdw/rdw rats.
  • Megumi Okumura, Kumiko Yoshimatsu, Sanit Kumperasart, Ichiro Nakamura, Michiko Ogino, Midori Taruishi, Araya Sungdee, Sirima Pattamadilok, Ima Nurisa Ibrahim, Sri Erlina, Takashi Agui, Richard Yanagihara, Jiro Arikawa CLINICAL AND VACCINE IMMUNOLOGY 14 (2) 173 -181 2007年02月 [査読無し][通常論文]
     
    Thottapalayam virus (TPMV), a member of the genus Hantavirus in the family Bunyaviridae, was isolated from an insectivore, Suncus murinus (musk shrew), captured in southern India in 1964. While the isolation of TPMV predates the discovery of the prototype Hantaan virus, little is known about its genetics and biology. To date, preliminary evidence suggests that TPMV differs significantly, both antigenically and genetically, from all known rodent-borne hantaviruses. However, since detailed epizootiological studies have not been conducted, it is unclear if TPMV is naturally harbored by an insectivore host or if TPMV represents a "spillover" from its natural rodent reservoir host. Moreover, to what extent TPMV causes infection and/or disease in humans is not known. To address these issues, we first studied the antigenic profile of TPMV using monoclonal antibodies against Hantaan and Seoul viruses and pollyclonal immune sera against Puumala virus and TPMV. Armed with this newfound information, we developed an enzyme-linked immunosorbent assay system for the diagnosis of TPMV infections in shrews and humans, using a recombinant TPMV N antigen manipulated to have an E5/G6 epitope to be captured by monoclonal antibody clone E5/G6. Using this assay, we found anti-TPMV antibodies in sera from a patient with high fever of unknown etiology in Thailand and from two shrews captured in Indonesia. Seropositivity was verified by the indirect immunofluorescence antibody test, Western blotting analysis, and focus reduction neutralization test. Collectively, our data indicate that TPMV is harbored by Suncus murinus as its host in nature and is capable of infecting humans.
  • Megumi Okumura, Kumiko Yoshimatsu, Sanit Kumperasart, Ichiro Nakamura, Michiko Ogino, Midori Taruishi, Araya Sungdee, Sirima Pattamadilok, Ima Nurisa Ibrahim, Sri Erlina, Takashi Agui, Richard Yanagihara, Jiro Arikawa CLINICAL AND VACCINE IMMUNOLOGY 14 (2) 173 -181 2007年02月 [査読無し][通常論文]
     
    Thottapalayam virus (TPMV), a member of the genus Hantavirus in the family Bunyaviridae, was isolated from an insectivore, Suncus murinus (musk shrew), captured in southern India in 1964. While the isolation of TPMV predates the discovery of the prototype Hantaan virus, little is known about its genetics and biology. To date, preliminary evidence suggests that TPMV differs significantly, both antigenically and genetically, from all known rodent-borne hantaviruses. However, since detailed epizootiological studies have not been conducted, it is unclear if TPMV is naturally harbored by an insectivore host or if TPMV represents a "spillover" from its natural rodent reservoir host. Moreover, to what extent TPMV causes infection and/or disease in humans is not known. To address these issues, we first studied the antigenic profile of TPMV using monoclonal antibodies against Hantaan and Seoul viruses and pollyclonal immune sera against Puumala virus and TPMV. Armed with this newfound information, we developed an enzyme-linked immunosorbent assay system for the diagnosis of TPMV infections in shrews and humans, using a recombinant TPMV N antigen manipulated to have an E5/G6 epitope to be captured by monoclonal antibody clone E5/G6. Using this assay, we found anti-TPMV antibodies in sera from a patient with high fever of unknown etiology in Thailand and from two shrews captured in Indonesia. Seropositivity was verified by the indirect immunofluorescence antibody test, Western blotting analysis, and focus reduction neutralization test. Collectively, our data indicate that TPMV is harbored by Suncus murinus as its host in nature and is capable of infecting humans.
  • AR Cho, K Uchio-Yamada, T Torigai, T Miyamoto, Miyoshi, I, J Matsuda, T Kurosawa, Y Kon, A Asano, N Sasaki, T Agui MAMMALIAN GENOME 17 (5) 407 -416 2006年05月 [査読無し][通常論文]
     
    The ICGN mouse is a model for nephrotic syndrome (NS) which presents with proteinuria, hyperlipidemia, and edema. In this study we attempted to identify the gene(s) responsible for NS. By analyzing albuminuria in 160 (ICGN x MSM)F-1 x ICGN backcross progenies, we found that NS in the ICGN mouse is caused by more than one gene. We then performed a quantitative trait locus (QTL) analysis and detected a QTL with a very high LOD score peak in the telomeric region of Chr 15. By analyzing the nucleotide sequence of 22 genes located close to the QTL, we found that the tensin2 gene of the ICGN mouse possessed an 8-nucleotide deletion mutation in exon 18, leading to a frameshift and giving rise to a terminal codon at a premature position. Analyses of in situ hybridization and immunohistochemistry revealed that tensin2 was expressed in podocytes and tubular epithelial cells in normal mice but not in the ICGN mouse. These data raise the possibility that a mutation of the tensin2 gene is responsible for NS of the ICGN mouse and tensin2 is a prerequisite for the normal kidney function.
  • AR Cho, K Uchio-Yamada, T Torigai, T Miyamoto, Miyoshi, I, J Matsuda, T Kurosawa, Y Kon, A Asano, N Sasaki, T Agui MAMMALIAN GENOME 17 (5) 407 -416 2006年05月 [査読無し][通常論文]
     
    The ICGN mouse is a model for nephrotic syndrome (NS) which presents with proteinuria, hyperlipidemia, and edema. In this study we attempted to identify the gene(s) responsible for NS. By analyzing albuminuria in 160 (ICGN x MSM)F-1 x ICGN backcross progenies, we found that NS in the ICGN mouse is caused by more than one gene. We then performed a quantitative trait locus (QTL) analysis and detected a QTL with a very high LOD score peak in the telomeric region of Chr 15. By analyzing the nucleotide sequence of 22 genes located close to the QTL, we found that the tensin2 gene of the ICGN mouse possessed an 8-nucleotide deletion mutation in exon 18, leading to a frameshift and giving rise to a terminal codon at a premature position. Analyses of in situ hybridization and immunohistochemistry revealed that tensin2 was expressed in podocytes and tubular epithelial cells in normal mice but not in the ICGN mouse. These data raise the possibility that a mutation of the tensin2 gene is responsible for NS of the ICGN mouse and tensin2 is a prerequisite for the normal kidney function.
  • Analysis of the cell cycle of fibroblasts derived from the LEC rat after X-irradiation.
    Jpn. J. Vet. Res. 53 141 -148 2006年 [査読無し][通常論文]
  • Analysis of the cell cycle of fibroblasts derived from the LEC rat after X-irradiation.
    Jpn. J. Vet. Res. 53 141 -148 2006年 [査読無し][通常論文]
  • T Nakamura, A Asano, S Okano, JH Ko, Y Kon, T Watanabe, T Agui JOURNAL OF INTERFERON AND CYTOKINE RESEARCH 25 (3) 169 -173 2005年03月 [査読無し][通常論文]
     
    Mx is an interferon (IFN)-induced protein that shows antiviral activities against RNA viruses. We examined an expression of mRNA, an intracellular localization of protein, and an antiviral property of canine Mx1 and Mx2. Both Mx1 and Mx2 mRNAs were induced in a canine kidney cell line Madin-Darby canine kidney (MDCK), stimulated with an IFN-inducer, poly(I) (.) poly(C) for 12 h, suggesting the presence of regulatory mechanisms consistent with Mx genes in other species. By immunostaining BALB/3T3 fibroblasts transiently transfected FLAG epitope-tagged canine Mx1 and Mx2 cDNAs with an anti-FLAG tag, it was revealed that both Mx1 and Mx2 proteins are localized in cytoplasm. BALB/3T3 fibroblasts expressing stably Mx2 but not Mx1 had an antiviral activity against recombinant vesicular stomatitis virus (VSV). This is the first report demonstrating the functional analysis of canine Mx proteins.
  • T Nakamura, A Asano, S Okano, JH Ko, Y Kon, T Watanabe, T Agui JOURNAL OF INTERFERON AND CYTOKINE RESEARCH 25 (3) 169 -173 2005年03月 [査読無し][通常論文]
     
    Mx is an interferon (IFN)-induced protein that shows antiviral activities against RNA viruses. We examined an expression of mRNA, an intracellular localization of protein, and an antiviral property of canine Mx1 and Mx2. Both Mx1 and Mx2 mRNAs were induced in a canine kidney cell line Madin-Darby canine kidney (MDCK), stimulated with an IFN-inducer, poly(I) (.) poly(C) for 12 h, suggesting the presence of regulatory mechanisms consistent with Mx genes in other species. By immunostaining BALB/3T3 fibroblasts transiently transfected FLAG epitope-tagged canine Mx1 and Mx2 cDNAs with an anti-FLAG tag, it was revealed that both Mx1 and Mx2 proteins are localized in cytoplasm. BALB/3T3 fibroblasts expressing stably Mx2 but not Mx1 had an antiviral activity against recombinant vesicular stomatitis virus (VSV). This is the first report demonstrating the functional analysis of canine Mx proteins.
  • Y Namiki, Y Kon, K Kazusa, A Asano, N Sasaki, T Agui MAMMALIAN GENOME 16 (2) 96 -102 2005年02月 [査読無し][通常論文]
     
    The MRL/MpJ mouse has previously been reported to possess an interesting phenotype in which spermatocytes are resistant to the abdominal temperature heat shock. In this study genetic analysis for it was performed. The phenotypes of F-2 progenies produced by mating MRL/MpJ and control strain C57BL/6 mice were not segregated into two types as parental phenotypes, suggesting that the phenotype is controlled by multiple genetic loci. Thus, quantitative trait loci (QTL) analysis was performed using 98 microsatellite markers. The weight ratio of the cryptorchid testis to the intact testis (testis weight ratio) and the Sertoli cell index were used for quantitative traits. QTL analysis revealed two significant QTLs located on Chrs 1 and 11 for testis weight ratio and one significant QTL located in the same region of Chr 1 for the Sertoli cell index. A microsatellite marker locus located in the peak of the QTL on Chr 1 did not recombine with the exonuclease 1 (Exo1) gene locus in 140 F-2 progenies. Mutation of the Exo1 gene was previously reported to be responsible for metaphase-specific apoptosis (MSA) of spermatocytes in the MRL/MpJ mouse. These results raise the possibility that mutation of the Exo1 gene is responsible for both MSA and heat stress resistance of spermatocytes in the MRL/MpJ mouse.
  • Y Namiki, Y Kon, K Kazusa, A Asano, N Sasaki, T Agui MAMMALIAN GENOME 16 (2) 96 -102 2005年02月 [査読無し][通常論文]
     
    The MRL/MpJ mouse has previously been reported to possess an interesting phenotype in which spermatocytes are resistant to the abdominal temperature heat shock. In this study genetic analysis for it was performed. The phenotypes of F-2 progenies produced by mating MRL/MpJ and control strain C57BL/6 mice were not segregated into two types as parental phenotypes, suggesting that the phenotype is controlled by multiple genetic loci. Thus, quantitative trait loci (QTL) analysis was performed using 98 microsatellite markers. The weight ratio of the cryptorchid testis to the intact testis (testis weight ratio) and the Sertoli cell index were used for quantitative traits. QTL analysis revealed two significant QTLs located on Chrs 1 and 11 for testis weight ratio and one significant QTL located in the same region of Chr 1 for the Sertoli cell index. A microsatellite marker locus located in the peak of the QTL on Chr 1 did not recombine with the exonuclease 1 (Exo1) gene locus in 140 F-2 progenies. Mutation of the Exo1 gene was previously reported to be responsible for metaphase-specific apoptosis (MSA) of spermatocytes in the MRL/MpJ mouse. These results raise the possibility that mutation of the Exo1 gene is responsible for both MSA and heat stress resistance of spermatocytes in the MRL/MpJ mouse.
  • M Okumura, K Yoshimatsu, K Araki, BH Lee, A Asano, T Agui, J Arikawa ARCHIVES OF VIROLOGY 149 (12) 2427 -2434 2004年12月 [査読無し][通常論文]
     
    Monoclonal antibody E5/G6 recognized a linear epitope common to hantavirus nucleocapsid proteins. Using synthetic peptides, we identified epitope E5/G6 as the 9 merYEDVNGIRK (NP 165 - 173), in which D167, G170, I171, and R172 are indispensable. Furthermore, all the peptides synthesized using various hantavirus sequences bound MAb E5/G6 consistently, despite the existence of several amino acid variations in this region. These results indicate that MAb E5/G6 is a useful tool for detecting hantavirus antigen in rodent or patient tissues using Western blotting or other immunohistochemical assays.
  • M Okumura, K Yoshimatsu, K Araki, BH Lee, A Asano, T Agui, J Arikawa ARCHIVES OF VIROLOGY 149 (12) 2427 -2434 2004年12月 [査読無し][通常論文]
     
    Monoclonal antibody E5/G6 recognized a linear epitope common to hantavirus nucleocapsid proteins. Using synthetic peptides, we identified epitope E5/G6 as the 9 merYEDVNGIRK (NP 165 - 173), in which D167, G170, I171, and R172 are indispensable. Furthermore, all the peptides synthesized using various hantavirus sequences bound MAb E5/G6 consistently, despite the existence of several amino acid variations in this region. These results indicate that MAb E5/G6 is a useful tool for detecting hantavirus antigen in rodent or patient tissues using Western blotting or other immunohistochemical assays.
  • K Kazusa, Y Namiki, A Asano, Y Kon, D Endoh, T Agui COMPARATIVE MEDICINE 54 (2) 179 -184 2004年04月 [査読無し][通常論文]
     
    The purpose of the study reported here was to define strain differences in spermatogenesis in cryptorchid testes in mice. Mice of strains AM, BALB/c, CBA/N, C3H/He, C57BL/6 (136), ddY and ICR were found to be sensitive to heat stress attributable to experimentally induced cryptorchidism. In contrast, mice of strains AKR/N (AKR), MRL/MpJ-+/+ (M+) and MRL/MpJ-lpr/lpr (lpr) were resistant to heat stress. Relative increases of apoptotic cells were detected in the sensitive group, but not in the resistant group. A decrease of proliferating cell nuclear antigen-immunoreactive cells after experimentally induced cryptorchidism was observed only in the sensitive group. These results suggested that heat stress-resistant germ cells were present in MRL and AKR strains, possibly originating from the genetic background.
  • JH Ko, A Takada, T Mitsuhashi, T Agui, T Watanabe ANIMAL GENETICS 35 (2) 119 -122 2004年04月 [査読無し][通常論文]
     
    An attempt was made to determine whether amino acid variation at position 631 in the chicken Mx protein definitely influences antiviral specificity, using an artificial mutation technique by which a single amino acid was reciprocally substituted between Ser (AGT) and Asn (AAT) at position 631 of the negative and positive chicken Mx, respectively. Using permanently transfected 3T3 cell lines, the antiviral potential of chicken Mx against vesicular stomatitis virus infection was analysed. The results indicated that the phenotype of antiviral activity depends on the amino acid difference at position 631; that is, the genotype coding Asn at position 631 corresponds to the positive antiviral phenotype, and the genotype coding Ser corresponds to the negative phenotype. The present study has confirmed that the antiviral specificity of chicken Mx protein is determined by an amino acid substitution at the carboxy terminus.
  • K Kazusa, Y Namiki, A Asano, Y Kon, D Endoh, T Agui COMPARATIVE MEDICINE 54 (2) 179 -184 2004年04月 [査読無し][通常論文]
     
    The purpose of the study reported here was to define strain differences in spermatogenesis in cryptorchid testes in mice. Mice of strains AM, BALB/c, CBA/N, C3H/He, C57BL/6 (136), ddY and ICR were found to be sensitive to heat stress attributable to experimentally induced cryptorchidism. In contrast, mice of strains AKR/N (AKR), MRL/MpJ-+/+ (M+) and MRL/MpJ-lpr/lpr (lpr) were resistant to heat stress. Relative increases of apoptotic cells were detected in the sensitive group, but not in the resistant group. A decrease of proliferating cell nuclear antigen-immunoreactive cells after experimentally induced cryptorchidism was observed only in the sensitive group. These results suggested that heat stress-resistant germ cells were present in MRL and AKR strains, possibly originating from the genetic background.
  • JH Ko, A Takada, T Mitsuhashi, T Agui, T Watanabe ANIMAL GENETICS 35 (2) 119 -122 2004年04月 [査読無し][通常論文]
     
    An attempt was made to determine whether amino acid variation at position 631 in the chicken Mx protein definitely influences antiviral specificity, using an artificial mutation technique by which a single amino acid was reciprocally substituted between Ser (AGT) and Asn (AAT) at position 631 of the negative and positive chicken Mx, respectively. Using permanently transfected 3T3 cell lines, the antiviral potential of chicken Mx against vesicular stomatitis virus infection was analysed. The results indicated that the phenotype of antiviral activity depends on the amino acid difference at position 631; that is, the genotype coding Asn at position 631 corresponds to the positive antiviral phenotype, and the genotype coding Ser corresponds to the negative phenotype. The present study has confirmed that the antiviral specificity of chicken Mx protein is determined by an amino acid substitution at the carboxy terminus.
  • Characterization of the chicken PKR:Polymorphism of the gene and antiviral activity against vesicular stomatitis virus.
    Jpn. J. Vet. Res., 51 123 -133 2004年 [査読無し][通常論文]
  • J. Vet. Med. Sci. 66 (12) 1523 -1528 2004年 [査読無し][通常論文]
  • Characterization of the chicken PKR:Polymorphism of the gene and antiviral activity against vesicular stomatitis virus.
    Jpn. J. Vet. Res., 51 123 -133 2004年 [査読無し][通常論文]
  • Atsushi ASANO, Yasuhiro KON, Takashi AGUI J. Vet. Med. Sci. 66 (12) 1523 -1528 2004年 [査読無し][通常論文]
  • Investigation of post-transcriptional events of the thyroglobulin in the thyroid gland of the hypothyroid growth-retarded mouse DW/J-grt
    Nagoya Med. J. 45 133 -143 2002年 [査読無し][通常論文]
  • Investigation of post-transcriptional events of the thyroglobulin in the thyroid gland of the hypothyroid growth-retarded mouse DW/J-grt
    Nagoya Med. J. 45 133 -143 2002年 [査読無し][通常論文]
  • Exp. Anim. 50 (2) 147 -151 2001年 [査読無し][通常論文]
  • Exp. Anim. 50 (4) 353 -354 2001年 [査読無し][通常論文]
  • Takashi AGUI, Tomomi MIYAMOTO, Takashi TSUMAGARI Exp. Anim. 50 (2) 147 -151 2001年 [査読無し][通常論文]
  • Cha-Gyun JUNG, Tomomi MIYAMOTO, Takashi TSUMAGARI, Takashi AGUI Exp. Anim. 50 (4) 337 -340 2001年 [査読無し][通常論文]
  • Kazuhiko MASUDA, Tomomi MIYAMOTO, Cha-Gyun JUNG, Ming DING, Ji-Ming CHENG, Takashi TSUMAGARI, Tadao MANABE, Takashi AGUI Exp. Anim. 50 (4) 353 -354 2001年 [査読無し][通常論文]
  • PS Kim, M Ding, S Menon, CG Jung, JM Cheng, T Miyamoto, BL Li, T Agui MOLECULAR ENDOCRINOLOGY 14 (12) 1944 -1953 2000年12月 [査読無し][通常論文]
     
    A convincing line of evidence is being developed that the congenital nongoitrous hypothyroidism and dwarfism observed in the WIC-rdw rat may indeed be caused by a primary defect in thyroid hormonogenesis. in support of this hypothesis, several recent reports have shown the presence of elevated molecular chaperone levels in the WIC-rdw thyrocytes, the endoplasmic reticulum of which was markedly dilated, suggesting a defect in intracellular protein transport. Here the studies were undertaken to identify the precise molecular defect in the WIC-rdw rat. First, the genetic linkage analysis revealed that the rdw locus was on rat chromosome 7 and was identical to the thyroglobulin (Tg) gene locus. Moreover, the Tg protein level was reduced in the WIC-rdw thyroid despite a similar level of the Tg gene transcripts that were indistinguishable in their size from the normal. Next, the complete sequencing of the rdw and the normal rat Tg cDNAs revealed a single nucleotide change, G6958C, resulting in a G2320R missense mutation in a highly conserved region of the Tg molecule. Finally, transient expression of the intact Tg cDNA containing the rdw mutation in the COS-7 cells showed no detectable Tg in the secreted media, indicating a severe defect in the export of the mutant Tg. Together, our observations suggest that a missense mutation, G2320R, in the Tg gene is responsible for the rdw mutation in the WIC-rdw rat.
  • PS Kim, M Ding, S Menon, CG Jung, JM Cheng, T Miyamoto, BL Li, T Agui MOLECULAR ENDOCRINOLOGY 14 (12) 1944 -1953 2000年12月 [査読無し][通常論文]
     
    A convincing line of evidence is being developed that the congenital nongoitrous hypothyroidism and dwarfism observed in the WIC-rdw rat may indeed be caused by a primary defect in thyroid hormonogenesis. in support of this hypothesis, several recent reports have shown the presence of elevated molecular chaperone levels in the WIC-rdw thyrocytes, the endoplasmic reticulum of which was markedly dilated, suggesting a defect in intracellular protein transport. Here the studies were undertaken to identify the precise molecular defect in the WIC-rdw rat. First, the genetic linkage analysis revealed that the rdw locus was on rat chromosome 7 and was identical to the thyroglobulin (Tg) gene locus. Moreover, the Tg protein level was reduced in the WIC-rdw thyroid despite a similar level of the Tg gene transcripts that were indistinguishable in their size from the normal. Next, the complete sequencing of the rdw and the normal rat Tg cDNAs revealed a single nucleotide change, G6958C, resulting in a G2320R missense mutation in a highly conserved region of the Tg molecule. Finally, transient expression of the intact Tg cDNA containing the rdw mutation in the COS-7 cells showed no detectable Tg in the secreted media, indicating a severe defect in the export of the mutant Tg. Together, our observations suggest that a missense mutation, G2320R, in the Tg gene is responsible for the rdw mutation in the WIC-rdw rat.
  • T Agui, T Miyamoto, CG Jung, T Tsumagari, K Masuda, T Manabe MAMMALIAN GENOME 11 (10) 862 -865 2000年10月 [査読無し][通常論文]
     
    The LEC rat has been reported to exhibit X-ray hyper sensitivity and deficiency in DNA double-strand break (DSB) repair. The present study was performed to map the locus responsible for this phenotype, the xhs (X-ray hypersensitivity), as the first step in identifying the responsible gene. Analysis of the progeny of (BN x LEC)F-1 x LEC backcrosses indicated that the X-ray hypersensitive phenotype was controlled by multiple genetic loci in contrast to the results reported previously. Quantitative trait loci (QTL) linkage analysis revealed two responsible loci located on Chromosomes (Chr) 4 and 1. QTL on Chr 4 exhibited very strong linkage to the X-ray hypersensitive phenotype, while QTL on Chr 1 showed weak linkage. The Rad52 locus, mutation of which results in hypersensitivity to ionizing radiation and impairment of DNA DSB repair in yeast, was reported to be located on the synteneic regions of mouse Chr 6 and human Chr 12. However, mapping of the rat Rad52 locus indicated that it was located 23 cM distal to the QTL on Chr 4. Furthermore, none of the radiosensitivity-related loci mapped previously in the rat chromosome were identical to the QTL on Chrs 4 and 1 in the LEC rat. Thus, it seems that X-ray hypersensitivity in the LEC rat is caused by mutation(s) in as-yet-undefined genes.
  • M Nakanishi, H Ando, N Watanabe, K Kitamura, K Ito, H Okayama, T Miyamoto, T Agui, M Sasaki GENES TO CELLS 5 (10) 839 -847 2000年10月 [査読無し][通常論文]
     
    Background: In eukaryotic cells, the kinase activity of the mitosis-promoting complex composed of cyclin B and Cdc2 (Cdk1) is negatively regulated by the phosphorylation of Cdk1 on threonine or tyrosine residues within its ATP binding domain. Results: We identified human Wee1B by searching a sequence database. The predicted human Wee1B protein comprises 561 amino acids. Northern blot analysis revealed that human Wee1B mRNA is particularly abundant in testis. Interestingly, RT-PCR using early embryos revealed that the Wee1B product was readily detectable at the mature oocyte, but abruptly disappeared at embryonic day 2.5, suggesting that the amount of Wee1B mRNA is dependent on the maternal expression. GFP-Wee1B showed a predominantly nuclear localization in HeLa cells. Human Wee1B was able to rescue the lethal phenotype of the fission yeast wee1-50 Delta mik1 mutant, and over-expression of the human protein in these cells resulted in cell elongation as a result of arrest of the cell cycle at the G(2)-M transition. Recombinant Wee1B effectively phosphorylated cyclin B-associated Cdk1 on tyrosine-15, resulting in an inactivation of the kinase activity of Cdk1. Conclusion: We identified human Wee1B as a novel Cdk1-inhibitory kinase. The identification of this new member of the Wee1 family suggests that inhibition of Cdk1 is mediated at multiple levels in mammals.
  • T Agui, T Miyamoto, CG Jung, T Tsumagari, K Masuda, T Manabe MAMMALIAN GENOME 11 (10) 862 -865 2000年10月 [査読無し][通常論文]
     
    The LEC rat has been reported to exhibit X-ray hyper sensitivity and deficiency in DNA double-strand break (DSB) repair. The present study was performed to map the locus responsible for this phenotype, the xhs (X-ray hypersensitivity), as the first step in identifying the responsible gene. Analysis of the progeny of (BN x LEC)F-1 x LEC backcrosses indicated that the X-ray hypersensitive phenotype was controlled by multiple genetic loci in contrast to the results reported previously. Quantitative trait loci (QTL) linkage analysis revealed two responsible loci located on Chromosomes (Chr) 4 and 1. QTL on Chr 4 exhibited very strong linkage to the X-ray hypersensitive phenotype, while QTL on Chr 1 showed weak linkage. The Rad52 locus, mutation of which results in hypersensitivity to ionizing radiation and impairment of DNA DSB repair in yeast, was reported to be located on the synteneic regions of mouse Chr 6 and human Chr 12. However, mapping of the rat Rad52 locus indicated that it was located 23 cM distal to the QTL on Chr 4. Furthermore, none of the radiosensitivity-related loci mapped previously in the rat chromosome were identical to the QTL on Chrs 4 and 1 in the LEC rat. Thus, it seems that X-ray hypersensitivity in the LEC rat is caused by mutation(s) in as-yet-undefined genes.
  • M Nakanishi, H Ando, N Watanabe, K Kitamura, K Ito, H Okayama, T Miyamoto, T Agui, M Sasaki GENES TO CELLS 5 (10) 839 -847 2000年10月 [査読無し][通常論文]
     
    Background: In eukaryotic cells, the kinase activity of the mitosis-promoting complex composed of cyclin B and Cdc2 (Cdk1) is negatively regulated by the phosphorylation of Cdk1 on threonine or tyrosine residues within its ATP binding domain. Results: We identified human Wee1B by searching a sequence database. The predicted human Wee1B protein comprises 561 amino acids. Northern blot analysis revealed that human Wee1B mRNA is particularly abundant in testis. Interestingly, RT-PCR using early embryos revealed that the Wee1B product was readily detectable at the mature oocyte, but abruptly disappeared at embryonic day 2.5, suggesting that the amount of Wee1B mRNA is dependent on the maternal expression. GFP-Wee1B showed a predominantly nuclear localization in HeLa cells. Human Wee1B was able to rescue the lethal phenotype of the fission yeast wee1-50 Delta mik1 mutant, and over-expression of the human protein in these cells resulted in cell elongation as a result of arrest of the cell cycle at the G(2)-M transition. Recombinant Wee1B effectively phosphorylated cyclin B-associated Cdk1 on tyrosine-15, resulting in an inactivation of the kinase activity of Cdk1. Conclusion: We identified human Wee1B as a novel Cdk1-inhibitory kinase. The identification of this new member of the Wee1 family suggests that inhibition of Cdk1 is mediated at multiple levels in mammals.
  • CC Jung, T Kamiyama, T Agui IMMUNOLOGY 98 (4) 590 -594 1999年12月 [査読無し][通常論文]
     
    Thymocytes and peripheral lymphocytes of BioBreeding (BB) diabetes-prone (BBDP) and diabetes-resistant (BBDR) rat were analysed by fluorescence-activated cell sorter (FACS). The number of CD4(-) CD8(-), CD4(+) CD8(-), CD4(-) CD8(+) and CD4(+) CD8(+) subsets was not different between BBDP and BBDR rat thymocytes, whereas spleen and lymph nodes in BBDP rats undergo severe T-cell lymphopenia. Notably, mature CD4(-) CD8(+) [T-cell receptor (TCR)-alpha beta(+) and CD5(+)] cells are certainly present in the BBDP rat thymus, unlike some previous reports, suggesting that the differentiation of CD4(-) CD8(+) from CD4(+) CD8(-) cells occurs normally in the BBDP rat thymus. As a cause of peripheral T-cell lymphopenia we suspected apoptosis of recent thymic emigrants. By FAGS analysis with fluorescein isothiocyanate-labelled annexin V, elevated apoptosis was evident in BBDP rat peripheral lymphocytes. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) staining in BBDP rat splenic sections revealed that a number of TUNEL-positive cells were observed in the T-lymphocyte-rich area. From these results, we postulate that an abnormally elevated apoptosis of peripheral T lymphocytes, but not impaired thymocyte differentiation, is a cause of the peripheral T-cell lymphopenia in BBDP rats.
  • CC Jung, T Kamiyama, T Agui IMMUNOLOGY 98 (4) 590 -594 1999年12月 [査読無し][通常論文]
     
    Thymocytes and peripheral lymphocytes of BioBreeding (BB) diabetes-prone (BBDP) and diabetes-resistant (BBDR) rat were analysed by fluorescence-activated cell sorter (FACS). The number of CD4(-) CD8(-), CD4(+) CD8(-), CD4(-) CD8(+) and CD4(+) CD8(+) subsets was not different between BBDP and BBDR rat thymocytes, whereas spleen and lymph nodes in BBDP rats undergo severe T-cell lymphopenia. Notably, mature CD4(-) CD8(+) [T-cell receptor (TCR)-alpha beta(+) and CD5(+)] cells are certainly present in the BBDP rat thymus, unlike some previous reports, suggesting that the differentiation of CD4(-) CD8(+) from CD4(+) CD8(-) cells occurs normally in the BBDP rat thymus. As a cause of peripheral T-cell lymphopenia we suspected apoptosis of recent thymic emigrants. By FAGS analysis with fluorescein isothiocyanate-labelled annexin V, elevated apoptosis was evident in BBDP rat peripheral lymphocytes. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) staining in BBDP rat splenic sections revealed that a number of TUNEL-positive cells were observed in the T-lymphocyte-rich area. From these results, we postulate that an abnormally elevated apoptosis of peripheral T lymphocytes, but not impaired thymocyte differentiation, is a cause of the peripheral T-cell lymphopenia in BBDP rats.
  • SAKAI T, AGUI T, KAICHUN W, OKA M, HISAEDA H, NAGASAWA H, HIMENO K, MATSUMOTO K Immunology 95 (2) 219 -225 1998年10月 [査読無し][通常論文]
     
    A mutant strain of rat, LEG, shows a novel arrest of T-c:ll maturation from CD4(+)8(+) to CD4(+)8(-), but not to CD4(-)8(+) cells in the thymus. The responsible mutant locus is designated the thid which was acted upon in a recessive manner of inheritance. We found that LEC rat thymocytes failed to respond to interleukin (IL)-1, IL-6 and IL-7 in the presence of the mitogenic lectins, Allo A or concanavalin A (Con A). The unresponsiveness appeared to be due to unresponsiveness to the lectin stimulation rather than because of cytokine stimulation. Normal rat CD4(-)8(+/-) (consisting of CD4(-)8(+) and CD4(-)8(-) thymocytes), CD4(+/-)8(-) (consisting of CD4(+)8(-) and CD4(-)8(-) thymocytes), and CD4(-)8(-) thymocyte subsets normally responded to mitogenic stimulation, while CD4(+)8(+) thymocytes did not. In contract, all LEC rat CD4(-)8(+/-), CD4(+/-)8(-), CB4(-)8(-) and CD4(-)8(+) thymocytes did not respond to the mitogenic stimulation, suggesting that the unresponsiveness of the CD4(-)8(+/-) thymocytes seems; to be responsible for the unresponsiveness of whole thymocytes in LEC rats. LEC rat CD4(-)8(+/-) thymocytes normally expressed Con A receptor (R), lymphocyte function-associated antigen-1 (LFA-1), and CD45, which are thought to be important molecules for lectin stimulation. When backcross rats from (F344 x LEC)F-1 x LEC were examined, the phenotype for the thid mutation correlated with the [H-3]thymidine deoxyribose (TdR) incorporation level in response to Con A stimulation; thymocytes from backcross rats showing +/thid phenotype responded to Con A stimulation normally, whereas thymocytes from backcross rats showing thid/thid phenotype showed significantly lower responsiveness compared with +/thid rats. However, in WKAH.C-thid congenic rat thymocytes that carry the thid mutation, the responsiveness to mitogenic stimulation was comparable to that of normal rat thymocytes. These results suggest that a defect in responsiveness to mitogenic stimulation in LEC rat thymocytes is controlled by multiple genetic loci and the thid locus is one of the important loci for the development of this abnormal phenotype.
  • T Sakai, T Agui, W Kaichun, M Oka, H Hisaeda, H Nagasawa, K Himeno, K Matsumoto IMMUNOLOGY 95 (2) 219 -225 1998年10月 [査読無し][通常論文]
     
    A mutant strain of rat, LEG, shows a novel arrest of T-c:ll maturation from CD4(+)8(+) to CD4(+)8(-), but not to CD4(-)8(+) cells in the thymus. The responsible mutant locus is designated the thid which was acted upon in a recessive manner of inheritance. We found that LEC rat thymocytes failed to respond to interleukin (IL)-1, IL-6 and IL-7 in the presence of the mitogenic lectins, Allo A or concanavalin A (Con A). The unresponsiveness appeared to be due to unresponsiveness to the lectin stimulation rather than because of cytokine stimulation. Normal rat CD4(-)8(+/-) (consisting of CD4(-)8(+) and CD4(-)8(-) thymocytes), CD4(+/-)8(-) (consisting of CD4(+)8(-) and CD4(-)8(-) thymocytes), and CD4(-)8(-) thymocyte subsets normally responded to mitogenic stimulation, while CD4(+)8(+) thymocytes did not. In contract, all LEC rat CD4(-)8(+/-), CD4(+/-)8(-), CB4(-)8(-) and CD4(-)8(+) thymocytes did not respond to the mitogenic stimulation, suggesting that the unresponsiveness of the CD4(-)8(+/-) thymocytes seems; to be responsible for the unresponsiveness of whole thymocytes in LEC rats. LEC rat CD4(-)8(+/-) thymocytes normally expressed Con A receptor (R), lymphocyte function-associated antigen-1 (LFA-1), and CD45, which are thought to be important molecules for lectin stimulation. When backcross rats from (F344 x LEC)F-1 x LEC were examined, the phenotype for the thid mutation correlated with the [H-3]thymidine deoxyribose (TdR) incorporation level in response to Con A stimulation; thymocytes from backcross rats showing +/thid phenotype responded to Con A stimulation normally, whereas thymocytes from backcross rats showing thid/thid phenotype showed significantly lower responsiveness compared with +/thid rats. However, in WKAH.C-thid congenic rat thymocytes that carry the thid mutation, the responsiveness to mitogenic stimulation was comparable to that of normal rat thymocytes. These results suggest that a defect in responsiveness to mitogenic stimulation in LEC rat thymocytes is controlled by multiple genetic loci and the thid locus is one of the important loci for the development of this abnormal phenotype.
  • M Oh-Ishi, A Omori, JY Kwon, T Agui, T Maeda, SI Furudate ENDOCRINOLOGY 139 (3) 1288 -1299 1998年03月 [査読無し][通常論文]
     
    Proteins having relations to hereditary dwarfism of the rdw rat (gene symbol: rdw) were searched for in various tissues of the rat with an improved two-dimensional gel electrophoresis technique followed by immunoblotting and microsequencing. Tissues inspected were cerebral cortex, cerebellum, brain trunk, hypothalamus, pituitary, thyroid gland, liver, testis, spleen, and thymus. Only pituitary and thyroid glands among those tissues showed abnormalities in protein contents. GH and PRL contents in the rdw pituitary were much less than in the normal one, which in the former were 1/15 and less than 1/30 times as much as in the latter, respectively, but the abnormalities in the rdw thyroid were far more serious than in the pituitary. At least 18 protein levels in the rdw thyroid were above, and 17 were below the normal. Those identified among the increased proteins were endoplasmin (GRP94), immunoglobulin heavy chain binding protein (BiP/GRP78), and heat shock protein 70 (hsp70), the contents of which respectively were 40 times, 10 times and more than 50 times as much in the rdw thyroid as in the normal tissue. Because BiP and endoplasmin are known to be ER resident proteins, and because all three belong to a chaperone protein family, accumulation of these proteins in the rdw thyroid suggests that protein folding and secreting disorders underlie the hypothyroidism of the rdw rat.
  • Endocrinology 139 1288 -1299 1998年 [査読無し][通常論文]
  • R Uchikawa, S Matsuda, M Yamada, M Nishida, T Agui, N Arizono PARASITE IMMUNOLOGY 19 (10) 461 -468 1997年10月 [査読無し][通常論文]
     
    Long-Evans Cinnamon (LEC) vats have maturational arrest of CD4(+)8(-) T cells from CD4(+)8(+) cells in the thymus. Despite this, CD4(+)8(-) T cells are always present in peripheral lymphoid organs of LEC rats, suggesting that these CD4(+)8(-) T cells are generated by an uncommon pathway. We investigated the role of LEC rat peripheral CD4(+)8(-) T cells in Th2-associated responses to infection with the nematode Nippostrongylus brasiliensis. After infection, the numbers of CD4(+)8(-) TCR alpha beta(+) T cells significantly increased in mesenteric lymph nones (MLN) and the spleen, while those in the thymus were still negligible. Infection also induced significant up-regulation of IL-4 gene expression in LEC rat MLN cells. Total serum IgE levels in LEC rats were markedly increased two weeks after infection. Mucosal mast cell responses in the gut and lungs of LEC rats were induced as prominently as in control Long-Evans Agouti (LEA) mts. Faecal egg count data indicated that LEC rats rejected nematodes faster than LEA rats. These results suggested that Th2-associated responses can be induced by nematode infection in LEC rats probably through the extrathymic recruitment and proliferation of CD4(+)8(-) TCR alpha beta(+) T cells.
  • YQ Cai, XN Xin, GJ Shim, Y Mokuno, H Uehara, T Yamada, T Agui, K Matsumoto ENDOCRINOLOGY 138 (6) 2515 -2520 1997年06月 [査読無し][通常論文]
     
    Regulation of Interleukin-6 (IL-6) production in bone marrow (BM)-derived stromal cells by neuropeptides, pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP), was examined. Both forms of PACAP, PACAP-27 and PACAP-38, as well as VIP significantly increased IL-6 production by rat BM-derived stromal cells at physiological concentrations ranging from 10(-10)-10(-8) M. The three related peptides (PACAP-27, -38, and VIP) stimulated the production of both cAMP and inositol 1,4,5-trisphosphate (IP3) in rat PM-derived stromal cells with similar 50% effective concentrations. The stimulatory potency of the three related peptides for the production of IL-6, cAMP, and IP3 was almost consistent, suggesting that the dual signaling transduction pathways may be involved in PACAP/VIP-induced IL-6 production in rat BM-derived stromal cells. The messenger RNA (mRNA) for the third subtype of PACAP receptor (PVR3) was found to be abundantly expressed in both PM-derived stromal cells and the BM tissue, whereas little of the mRNA for type 1 (PVR1) nor type 2 (PVRB) was detected. Furthermore, the mRNAs for PACAP and VIP were detected in the BM tissue, suggesting that both PACAP/VIP and PVR3 are synthesized in vivo in the BM. The results shown in this paper suggest that PACAP/VIP and their receptor play an important role in the IL-6 production and perhaps in the hematopoiesis in the BM.
  • YQ Cai, XN Xin, GJ Shim, Y Mokuno, H Uehara, T Yamada, T Agui, K Matsumoto ENDOCRINOLOGY 138 (6) 2515 -2520 1997年06月 [査読無し][通常論文]
     
    Regulation of Interleukin-6 (IL-6) production in bone marrow (BM)-derived stromal cells by neuropeptides, pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP), was examined. Both forms of PACAP, PACAP-27 and PACAP-38, as well as VIP significantly increased IL-6 production by rat BM-derived stromal cells at physiological concentrations ranging from 10(-10)-10(-8) M. The three related peptides (PACAP-27, -38, and VIP) stimulated the production of both cAMP and inositol 1,4,5-trisphosphate (IP3) in rat PM-derived stromal cells with similar 50% effective concentrations. The stimulatory potency of the three related peptides for the production of IL-6, cAMP, and IP3 was almost consistent, suggesting that the dual signaling transduction pathways may be involved in PACAP/VIP-induced IL-6 production in rat BM-derived stromal cells. The messenger RNA (mRNA) for the third subtype of PACAP receptor (PVR3) was found to be abundantly expressed in both PM-derived stromal cells and the BM tissue, whereas little of the mRNA for type 1 (PVR1) nor type 2 (PVRB) was detected. Furthermore, the mRNAs for PACAP and VIP were detected in the BM tissue, suggesting that both PACAP/VIP and PVR3 are synthesized in vivo in the BM. The results shown in this paper suggest that PACAP/VIP and their receptor play an important role in the IL-6 production and perhaps in the hematopoiesis in the BM.
  • T Sakai, T Agui, H Hisaeda, K Izumi, K Himeno, K Matsumoto JOURNAL OF TRACE ELEMENTS IN EXPERIMENTAL MEDICINE 10 (2) 81 -88 1997年 [査読無し][通常論文]
     
    A mutant strain of Long-Evans cinnamon (LEG) rats was found to have a novel defect in T-cell maturation, i.e., arrest of differentiation from CD4(+)8(+) to CD4(+)8(-), but not to CD4(-)8(+) thymocytes. Despite the maturational arrest of CD4(+)8(-) thymocytes, some CD4(+) T cells occurred in peripheral lymphoid organs in LEC rats. In the present study, expression of adhesion molecules was compared between normal and LEC rat T cells. Three-color flow cytometry analysis showed that the expression pattern of LFA-1 and LECAM-1 of LEC rat CD4(+) T cells was different from that of normal rat CD4(+) T cells; F344 rat CD4(+) T cells were LFA-1(+), LECAM-1(++), whereas LEC rat CD4(+) cells were LFA(-)1(++), LECAM-1(-). However, the expression pattern of these adhesion molecules on LEC rat CD8(+) T cells was the same as that on F344 rat CD8(+) T cells, suggesting that LEC rat T cells do not have an intrinsic defect in the expression of these molecules. To address the question of whether the abnormal expression of adhesion molecules is correlated with the thid mutation, we generated WKAH.C-thid congenic rats and analyzed these expression patterns. The expression of adhesion molecules on WKAH.C-thid congenic rat CD4(+) T cells was the same as that of WKAH rat CD4(+) T cells, suggesting that abnormal expression of adhesion molecules of LEC rat CD4(+) T cells is independent of the thid mutation. These results indicate that LEC rat CD4(+) T cells show a unique expression of adhesion molecules, and these phenotypes are independent of the thid mutation that causes maturational arrest of CD4(+)8(-) thymocytes. (C) 1997 Wiley-Liss, Inc.
  • Mapping of the grt locus to mouse Chromosome 5.
    Mamm. Genome 8 944 1997年 [査読無し][通常論文]
  • T Sakai, T Agui, H Hisaeda, K Izumi, K Himeno, K Matsumoto JOURNAL OF TRACE ELEMENTS IN EXPERIMENTAL MEDICINE 10 (2) 81 -88 1997年 [査読無し][通常論文]
     
    A mutant strain of Long-Evans cinnamon (LEG) rats was found to have a novel defect in T-cell maturation, i.e., arrest of differentiation from CD4(+)8(+) to CD4(+)8(-), but not to CD4(-)8(+) thymocytes. Despite the maturational arrest of CD4(+)8(-) thymocytes, some CD4(+) T cells occurred in peripheral lymphoid organs in LEC rats. In the present study, expression of adhesion molecules was compared between normal and LEC rat T cells. Three-color flow cytometry analysis showed that the expression pattern of LFA-1 and LECAM-1 of LEC rat CD4(+) T cells was different from that of normal rat CD4(+) T cells; F344 rat CD4(+) T cells were LFA-1(+), LECAM-1(++), whereas LEC rat CD4(+) cells were LFA(-)1(++), LECAM-1(-). However, the expression pattern of these adhesion molecules on LEC rat CD8(+) T cells was the same as that on F344 rat CD8(+) T cells, suggesting that LEC rat T cells do not have an intrinsic defect in the expression of these molecules. To address the question of whether the abnormal expression of adhesion molecules is correlated with the thid mutation, we generated WKAH.C-thid congenic rats and analyzed these expression patterns. The expression of adhesion molecules on WKAH.C-thid congenic rat CD4(+) T cells was the same as that of WKAH rat CD4(+) T cells, suggesting that abnormal expression of adhesion molecules of LEC rat CD4(+) T cells is independent of the thid mutation. These results indicate that LEC rat CD4(+) T cells show a unique expression of adhesion molecules, and these phenotypes are independent of the thid mutation that causes maturational arrest of CD4(+)8(-) thymocytes. (C) 1997 Wiley-Liss, Inc.
  • Ryuichi Uchikawa, Shinji Matsuda, Minoru Yamada, Minoru Nishida, Takashi Agui, Naoki Arizono Parasite Immunology 19 (10) 461 -468 1997年 [査読無し][通常論文]
     
    Long-Evans Cinnamon (LEC) rats have maturational arrest of CD4+8- T cells from CD4+8+ cells in the thymus. Despite this, CD4+8+ T cells are always present in peripheral lymphoid organs of LEC rats, suggesting that these CD4+8- T cells are generated by an uncommon pathways. We investigated the role of LEC rat peripheral CD4+8- T cells in Th2-associated responses to infection with the nematode Nippostrongylus brasiliensis. After infection, the numbers of CD4+8- TCRαβ+ T cells significantly increased in mesenteric lymph nodes (MLN) and the spleen, while those in the thymus were still negligible. Infection also induced significant up-regulation of IL-4 gene expression in LEC rat MLN cells. Total serum IgE levels in LEC rats were markedly increased two weeks after infection. Mucosal mast cell responses in the gut and lungs of LEC rats were induced as prominently as in control Long-Evans Agouti (LEA) rats. Faecal egg cont data indicated that LEC rats rejected nematodes faster than LEA rats. These results suggested that Th2-associated responses can be induced by nematode infection in LEC rats probably through the extrathymic recruitment and proliferation of CD4+8- TCRαβ+ T cells.
  • Mapping of the grt locus to mouse Chromosome 5.
    Mamm. Genome 8 944 1997年 [査読無し][通常論文]
  • J. Vet. Med. Sci. 58 1127 1996年 [査読無し][通常論文]
  • Abnormal splicing of the endothelin type B receptor mRNA in the aganglionosis rat.
    Nagoya Med. J. 40 193 -201 1996年 [査読無し][通常論文]
  • J. Vet. Med. Sci. 58 1127 1996年 [査読無し][通常論文]
  • Abnormal splicing of the endothelin type B receptor mRNA in the aganglionosis rat.
    Nagoya Med. J. 40 193 -201 1996年 [査読無し][通常論文]
  • T AGUI, XN XIN, YQ CAI, G SHIM, Y MURAMATSU, T YAMADA, H FUJIWARA, K MATSUMOTO J. Biochem. 118 (3) 500 -507 1995年09月 [査読無し][通常論文]
     
    The regulation of the gene expression of the atrial natriuretic peptide receptor (ANPR) subtypes, ANPR-A, ANPR-B, and ANPR-C, was investigated in a murine thymic stromal cell line, MRL 104.8a. When MRL 104.8a cells were cultured with transforming growth factor (TGF)-beta(1), [I-125]ANP binding sites increased with increasing dose of TGF-beta(1). These binding sites were identified as ANPR-C by a displacement experiment with ANPR-C-specific ligand, C-ANF, and by the affinity cross-linking of the [I-125] ANp binding sites with a chemical cross-linker to determine the molecular weight of the ANPR. This augmentation of the ANPR-C expression was elucidated to occur at the transcriptional level by Northern blot experiment, comparison of the relative amounts of mRNA by reverse transcription (RT)-PCR, and in vitro nuclear transcription assay. Conversely, the expression of the ANP biological receptors, ANPR-A and ANPR-B, was shown to be down-regulated by TGF-beta(1). These data suggest that TGF-beta(1) regulates the gene expression of ANPRs in the thymic stromal cells and that ANP and TGF-beta(1) might affect the thymic stromal cell functions.
  • T AGUI, XN XIN, YQ CAI, G SHIM, Y MURAMATSU, T YAMADA, H FUJIWARA, K MATSUMOTO JOURNAL OF BIOCHEMISTRY 118 (3) 500 -507 1995年09月 [査読無し][通常論文]
     
    The regulation of the gene expression of the atrial natriuretic peptide receptor (ANPR) subtypes, ANPR-A, ANPR-B, and ANPR-C, was investigated in a murine thymic stromal cell line, MRL 104.8a. When MRL 104.8a cells were cultured with transforming growth factor (TGF)-beta(1), [I-125]ANP binding sites increased with increasing dose of TGF-beta(1). These binding sites were identified as ANPR-C by a displacement experiment with ANPR-C-specific ligand, C-ANF, and by the affinity cross-linking of the [I-125] ANp binding sites with a chemical cross-linker to determine the molecular weight of the ANPR. This augmentation of the ANPR-C expression was elucidated to occur at the transcriptional level by Northern blot experiment, comparison of the relative amounts of mRNA by reverse transcription (RT)-PCR, and in vitro nuclear transcription assay. Conversely, the expression of the ANP biological receptors, ANPR-A and ANPR-B, was shown to be down-regulated by TGF-beta(1). These data suggest that TGF-beta(1) regulates the gene expression of ANPRs in the thymic stromal cells and that ANP and TGF-beta(1) might affect the thymic stromal cell functions.
  • Y CAI, T YAMADA, XIN, X, T AGUI, K MATSUMOTO ANIMAL GENETICS 26 (1) 39 -41 1995年02月 [査読無し][通常論文]
     
    Chromosomal assignments of the genes for rat endothelin receptor type A (ET(A)R) and type B (ET(B)R) were performed by analysing somatic cell hybrid DNAs with the polymerase chain reaction (PCR) using primers specific for rat ET(A)R and ET(B)R genes. The genes for ET(A)R and ET(B)R were assigned to rat chromosomes 19 and 15 respectively.
  • Y CAI, T YAMADA, XIN, X, T AGUI, K MATSUMOTO ANIMAL GENETICS 26 (1) 39 -41 1995年02月 [査読無し][通常論文]
     
    Chromosomal assignments of the genes for rat endothelin receptor type A (ET(A)R) and type B (ET(B)R) were performed by analysing somatic cell hybrid DNAs with the polymerase chain reaction (PCR) using primers specific for rat ET(A)R and ET(B)R genes. The genes for ET(A)R and ET(B)R were assigned to rat chromosomes 19 and 15 respectively.
  • XN XIN, YQ CAI, K MATSUMOTO, T AGUI ENDOCRINOLOGY 136 (1) 132 -137 1995年01月 [査読無し][通常論文]
     
    Endothelin (ET) produced by endothelial cells has recently been found to be a potent vasoconstricting hormone. In this paper, ET isopeptides, both ET-1 and ET-3, were shown to be potent stimulators of interleukin (IL)-6 production by a rat aortic endothelial cell clone, WAE-1. Semi-quantitative polymerase chain reaction analysis indicated that augmentation of IL-6 production is due to an increase in IL-6 messenger RNA level. Ligand binding assay indicated that most of the [I-125]ET-1 binding sites correspond to ET receptor type A (ET(A)R). However, ET receptor type B (ET(B)R) was shown to be also present on this cell Line by reverse transcription polymerase chain reaction using ET(B)R-specific primers and by ligand binding assay using [I-125]ET-3, although the protein receptor level is much lower than that of ET(A)R. ET-1, but not ET-3, induced inositol 1,4,5-triphosphate production and an increase in intracellular Ca2+ concentration with similar dose response. These data suggest that ET-1 stimulates IL-6 production through ET(A)R-phospholipase C activation axis, whereas ET-3 stimulates IL-6 production through different signaling pathway. The results shown in this paper raise the possibility that ET plays a role in inducing inflammation in endothelium.
  • 酒井 徹, 安居院 高志, 松村 陽治, 長澤 秀行, 姫野 國祐, 松本 耕三 J. Vet. Med. Sci. 57 (3) 527 -529 1995年 [査読無し][通常論文]
  • SAKAI T, AGUI T, MATSUMOTO K Eur. J. Immunol. 25 (5) 1399 -1404 1995年 [査読無し][通常論文]
  • The diversity of T cell receptor repertoire of peripheral CD4+ Iymphocytes in LEC rats.
    Immunol. Lett. 45 173 -177 1995年 [査読無し][通常論文]
  • XN XIN, YQ CAI, K MATSUMOTO, T AGUI ENDOCRINOLOGY 136 (1) 132 -137 1995年01月 [査読無し][通常論文]
     
    Endothelin (ET) produced by endothelial cells has recently been found to be a potent vasoconstricting hormone. In this paper, ET isopeptides, both ET-1 and ET-3, were shown to be potent stimulators of interleukin (IL)-6 production by a rat aortic endothelial cell clone, WAE-1. Semi-quantitative polymerase chain reaction analysis indicated that augmentation of IL-6 production is due to an increase in IL-6 messenger RNA level. Ligand binding assay indicated that most of the [I-125]ET-1 binding sites correspond to ET receptor type A (ET(A)R). However, ET receptor type B (ET(B)R) was shown to be also present on this cell Line by reverse transcription polymerase chain reaction using ET(B)R-specific primers and by ligand binding assay using [I-125]ET-3, although the protein receptor level is much lower than that of ET(A)R. ET-1, but not ET-3, induced inositol 1,4,5-triphosphate production and an increase in intracellular Ca2+ concentration with similar dose response. These data suggest that ET-1 stimulates IL-6 production through ET(A)R-phospholipase C activation axis, whereas ET-3 stimulates IL-6 production through different signaling pathway. The results shown in this paper raise the possibility that ET plays a role in inducing inflammation in endothelium.
  • Tohru SAKAI, Takashi AGUI, Yoji MURAMATSU, Hideyuki NAGASAWA, Kunisuke HIMENO, Kozo MATSUMOTO J. Vet. Med. Sci. 57 (3) 527 -529 1995年 [査読無し][通常論文]
  • The diversity of T cell receptor repertoire of peripheral CD4+ Iymphocytes in LEC rats.
    Immunol. Lett. 45 173 -177 1995年 [査読無し][通常論文]
  • T AGUI, XN XIN, YQ CAI, T SAKAI, K MATSUMOTO BLOOD 84 (8) 2531 -2538 1994年10月 [査読無し][通常論文]
     
    Endothelin (ET) produced by endothelial cells has recently been found to be a potent vasoconstricting hormone. In this report, ET is shown to be a potent stimulator of interleukin-6 (IL-6) production by rat bone marrow (BM)-derived stromal cells. It was also shown that ET increased the level of mRNA for IL-6 in these cells. The two types of ET receptor (R), ET(A)R and ET(B)R, were shown to be expressed on both BM-derived stromal cells in culture and ex vivo in BM tissue, suggesting that ET works as a physiologic stimulator of IL-6 production in the BM. It was shown that ET(A)R is coupled to phospholipase C activation, leading to the production of inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DAG) as second messengers in BM-derived stromal cells. This was corroborated by data showing that IL-6 production in these cells was induced by combined stimulation with ionomycin and phorbol myristate acetate, thereby bypassing the effects of IP3 and DAG. respectively. This is the first report on the hormonal regulation of IL-6 production by BM stromal cells, indicating that hematopoiesis is subject to endocrinologic regulation under physiologic conditions. ET has recently been reported to be produced by macrophages in response to bacterial lipopolysaccharide and human immunodeficiency virus-1 glycoprotein 120. These facts, taken together with our findings, raise the possibility that ET shares the same role of IL-1 as a local cytokine, mediating an intercellular signal between macrophages and BM stromal cells in response to bacterial or viral stimulation. (C) 1994 by The American Society of Hematology.
  • T AGUI, XN XIN, YQ CAI, T SAKAI, K MATSUMOTO BLOOD 84 (8) 2531 -2538 1994年10月 [査読無し][通常論文]
     
    Endothelin (ET) produced by endothelial cells has recently been found to be a potent vasoconstricting hormone. In this report, ET is shown to be a potent stimulator of interleukin-6 (IL-6) production by rat bone marrow (BM)-derived stromal cells. It was also shown that ET increased the level of mRNA for IL-6 in these cells. The two types of ET receptor (R), ET(A)R and ET(B)R, were shown to be expressed on both BM-derived stromal cells in culture and ex vivo in BM tissue, suggesting that ET works as a physiologic stimulator of IL-6 production in the BM. It was shown that ET(A)R is coupled to phospholipase C activation, leading to the production of inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DAG) as second messengers in BM-derived stromal cells. This was corroborated by data showing that IL-6 production in these cells was induced by combined stimulation with ionomycin and phorbol myristate acetate, thereby bypassing the effects of IP3 and DAG. respectively. This is the first report on the hormonal regulation of IL-6 production by BM stromal cells, indicating that hematopoiesis is subject to endocrinologic regulation under physiologic conditions. ET has recently been reported to be produced by macrophages in response to bacterial lipopolysaccharide and human immunodeficiency virus-1 glycoprotein 120. These facts, taken together with our findings, raise the possibility that ET shares the same role of IL-1 as a local cytokine, mediating an intercellular signal between macrophages and BM stromal cells in response to bacterial or viral stimulation. (C) 1994 by The American Society of Hematology.
  • T SAKAI, T AGUI, K MATSUMOTO IMMUNOLOGY LETTERS 41 (2-3) 185 -189 1994年07月 [査読無し][通常論文]
     
    LEC rat is a novel strain showing a maturational arrest from CD4(+8)+ to CD4(+)8(-) cells but not to CD4(-)8(+) cells in the thymus. In this study, we examined if this mutation affects the differentiation of intestinal intra-epithelial lymphocytes (IEL) in LEC rats. In normal rat IEL, all 4 subsets with respect to the CD4/ CD8 expression were observed. The CD4(-)8(+) population was dominant and a unique population, CD4(+)8(+), was observed as already shown in previous papers. Both CD4(+)8(-) and CD4(+)8(+) cells were CD3(+), TCR-alpha/beta(+), CD45RC(-), and CD5(+), whereas CD4(-)8(+) cells consisted of a heterogeneous population, being CD3(+), TCR-alpha/beta(+/-), CD45RC(+/-), and CD5(-). In LEC rat IEL, CD4(+)8(-) and CD4(+)8(+) cells existed normally and distribution of CD4/CD8 subsets was not different from that of normal rat IEL. Furthermore, the expression pattern of CD3, TCR-alpha/beta, CD45RC and CD5 was not different from that of normal rat IEL in each subset. These results suggest that maturational arrest of CD4(+)8(-) thymocytes does not affect IEL maturation, especially maturation of CD4(+)8(-) IEL, suggesting that the IEL maturation mechanism for CD4(+)8(-) cells is independent of that of thymocytes.
  • T SAKAI, T AGUI, K MATSUMOTO IMMUNOLOGY LETTERS 41 (2-3) 185 -189 1994年07月 [査読無し][通常論文]
     
    LEC rat is a novel strain showing a maturational arrest from CD4(+8)+ to CD4(+)8(-) cells but not to CD4(-)8(+) cells in the thymus. In this study, we examined if this mutation affects the differentiation of intestinal intra-epithelial lymphocytes (IEL) in LEC rats. In normal rat IEL, all 4 subsets with respect to the CD4/ CD8 expression were observed. The CD4(-)8(+) population was dominant and a unique population, CD4(+)8(+), was observed as already shown in previous papers. Both CD4(+)8(-) and CD4(+)8(+) cells were CD3(+), TCR-alpha/beta(+), CD45RC(-), and CD5(+), whereas CD4(-)8(+) cells consisted of a heterogeneous population, being CD3(+), TCR-alpha/beta(+/-), CD45RC(+/-), and CD5(-). In LEC rat IEL, CD4(+)8(-) and CD4(+)8(+) cells existed normally and distribution of CD4/CD8 subsets was not different from that of normal rat IEL. Furthermore, the expression pattern of CD3, TCR-alpha/beta, CD45RC and CD5 was not different from that of normal rat IEL in each subset. These results suggest that maturational arrest of CD4(+)8(-) thymocytes does not affect IEL maturation, especially maturation of CD4(+)8(-) IEL, suggesting that the IEL maturation mechanism for CD4(+)8(-) cells is independent of that of thymocytes.
  • M MIURA, T YAMADA, DH MORALEJO, T AGUI, J YAMADA, T SERIKAWA, K MATSUMOTO CYTOGENETICS AND CELL GENETICS 65 (1-2) 119 -121 1994年 [査読無し][通常論文]
     
    Chromosome assignments of the genes for rat ceruloplasmin (CP) and metallothionein (MT) were performed by analyzing somatic cell hybrid DNAs with the polymerase chain reaction (PCR), using primers specific for rat genes. The genes for CP and MT were assigned to rat chromosomes 2 and 19, respectively.
  • 酒井 徹, 安居院 高志, 三浦 みどり, 山田 宜永, 松本 耕三 J. Vet. Med. Sci. 56 (5) 883 -886 1994年 [査読無し][通常論文]
  • Mapping of the gene for rat endothelin-1 (Etl) to chromosome 17.
    Mamm. Genome 5 594 1994年 [査読無し][通常論文]
  • SASAKI N, HAYASHIZAKI Y, MURAMATSU M, MATSUDA Y, KURAMOTO T, AZUMA T, AGUI T, TAKEICHI N, KASAI N Biochem. Biophys. Res. Commun. 202 (1) 512 -518 1994年 [査読無し][通常論文]
  • SAKAI T, AGUI T, MATSUMOTO K Cell. Immunol. 158 (2) 414 -422 1994年 [査読無し][通常論文]
  • Morphological changes in rat aortic endothelial cell line stimulated by endothelin.
    Tokushima J. Exp. Med. 41 79 -86 1994年 [査読無し][通常論文]
  • M MIURA, T YAMADA, DH MORALEJO, T AGUI, J YAMADA, T SERIKAWA, K MATSUMOTO CYTOGENETICS AND CELL GENETICS 65 (1-2) 119 -121 1994年 [査読無し][通常論文]
     
    Chromosome assignments of the genes for rat ceruloplasmin (CP) and metallothionein (MT) were performed by analyzing somatic cell hybrid DNAs with the polymerase chain reaction (PCR), using primers specific for rat genes. The genes for CP and MT were assigned to rat chromosomes 2 and 19, respectively.
  • Tohru SAKAI, Takashi AGUI, Midori MIURA, Takahisa YAMADA, Kozo MATSUMOTO J. Vet. Med. Sci. 56 (5) 883 -886 1994年 [査読無し][通常論文]
  • Mapping of the gene for rat endothelin-1 (Etl) to chromosome 17.
    Mamm. Genome 5 594 1994年 [査読無し][通常論文]
  • Biochem. Biophys. Res. Commun. 202 (1) 512 -518 1994年 [査読無し][通常論文]
  • Morphological changes in rat aortic endothelial cell line stimulated by endothelin.
    Tokushima J. Exp. Med. 41 79 -86 1994年 [査読無し][通常論文]
  • JK KIM, T YAMADA, K SOGAWA, T AGUI, K MATSUMOTO RESEARCH COMMUNICATIONS IN CHEMICAL PATHOLOGY AND PHARMACOLOGY 81 (3) 369 -372 1993年09月 [査読無し][通常論文]
     
    Long-Evans Cinnamon (LEC) mutant rat, which spontaneously develops a chronically necrotizing hepatic injury at 4 months of age. exhibits an excess hepatic copper accumulation. DNA synthesis upon growth stimulation in LEC rat primary-cultured hepatocytes markedly decreased when compared to that of normal rat hepatocyte culture. Low response of DNA synthesis seems to be associated with nuclear disorganization induced by copper toxicity. However, LEC rat electrophoretic profile and content of each histone component responsible for DNA stability were indistinguishable from those of normal rat. These results suggest that copper-generated damage of substrates other than histones causes nuclear damage in LEC rat.
  • JK KIM, T YAMADA, K SOGAWA, T AGUI, K MATSUMOTO RESEARCH COMMUNICATIONS IN CHEMICAL PATHOLOGY AND PHARMACOLOGY 81 (3) 369 -372 1993年09月 [査読無し][通常論文]
     
    Long-Evans Cinnamon (LEC) mutant rat, which spontaneously develops a chronically necrotizing hepatic injury at 4 months of age. exhibits an excess hepatic copper accumulation. DNA synthesis upon growth stimulation in LEC rat primary-cultured hepatocytes markedly decreased when compared to that of normal rat hepatocyte culture. Low response of DNA synthesis seems to be associated with nuclear disorganization induced by copper toxicity. However, LEC rat electrophoretic profile and content of each histone component responsible for DNA stability were indistinguishable from those of normal rat. These results suggest that copper-generated damage of substrates other than histones causes nuclear damage in LEC rat.
  • T YAMADA, JK KIM, Y SUZUKI, T AGUI, K MATSUMOTO RESEARCH COMMUNICATIONS IN CHEMICAL PATHOLOGY AND PHARMACOLOGY 81 (2) 243 -246 1993年08月 [査読無し][通常論文]
     
    Long-Evans Cinnamon (LEC) mutant rat, which spontaneously develops a necrotizing hepatic injury at 4-5 months of age, exhibits an excess hepatic copper accumulation. Neotatal LEC rat showed higher ratio of cytosolic to noncytosolic copper contents than neonatal normal rat, suggesting that the efficiency of copper transportation into noncytosolic compartment is primarily inherently reduced in LEC rat. Additionally using northern blot analysis with neonates we suggested that the elevated metallothionein levels observed in adult LEC rat are probably secondary to elevated copper levels.
  • T YAMADA, JK KIM, Y SUZUKI, T AGUI, K MATSUMOTO RESEARCH COMMUNICATIONS IN CHEMICAL PATHOLOGY AND PHARMACOLOGY 81 (2) 243 -246 1993年08月 [査読無し][通常論文]
     
    Long-Evans Cinnamon (LEC) mutant rat, which spontaneously develops a necrotizing hepatic injury at 4-5 months of age, exhibits an excess hepatic copper accumulation. Neotatal LEC rat showed higher ratio of cytosolic to noncytosolic copper contents than neonatal normal rat, suggesting that the efficiency of copper transportation into noncytosolic compartment is primarily inherently reduced in LEC rat. Additionally using northern blot analysis with neonates we suggested that the elevated metallothionein levels observed in adult LEC rat are probably secondary to elevated copper levels.
  • T SAKAI, T AGUI, Y MURAMATSU, T YAMADA, K MATSUMOTO IMMUNOLOGY 79 (3) 491 -497 1993年07月 [査読無し][通常論文]
     
    A mutant strain of rat, LEC, exhibits a novel maturational arrest of T cells in the thymus, that is, an arrest of the differentiation from CD4+ CD8+ to CD4+ CD8- cells. However, CD4+ T cells were found to arise in lymph nodes (LN) of LEC rats. These CD4+ T cells were T-cell receptor (TcR)/CD3+ and the cross-linking of either TcR alone or both TcR and CD4 molecules induced [H-3]thymidine deoxyribose (TdR) incorporation, similar to functional CD4+ T cells. Stimulation with a T-cell mitogen, concanavalin A (Con A), also induced the [H-3]TdR incorporation and interleukin-2 receptor (IL-2R) expression in LEC rat CD4+ T cells. Nevertheless, Con A stimulation did not induce IL-2 production by these cells. However, when the stimulation signals were bypassed by ionomycin and phorbol 12-myristate 13-acetate (PMA), IL-2 was normally produced, suggesting that the IL-2 gene and nuclear factors for the IL-2 gene transcription are normal in LEC rats. These results suggest that signals induced by Con A are separated into the one for IL-2 secretion and the other for cell activation including DNA synthesis and IL-2R expression, and that the former signal transduction is blocked in LEC rat CD4+ T cells. Thus, CD4+ T cells in LEC rat LN might provide a good tool for investigating the regulatory mechanisms of IL-2 production.
  • T SAKAI, T AGUI, Y MURAMATSU, T YAMADA, K MATSUMOTO IMMUNOLOGY 79 (3) 491 -497 1993年07月 [査読無し][通常論文]
     
    A mutant strain of rat, LEC, exhibits a novel maturational arrest of T cells in the thymus, that is, an arrest of the differentiation from CD4+ CD8+ to CD4+ CD8- cells. However, CD4+ T cells were found to arise in lymph nodes (LN) of LEC rats. These CD4+ T cells were T-cell receptor (TcR)/CD3+ and the cross-linking of either TcR alone or both TcR and CD4 molecules induced [H-3]thymidine deoxyribose (TdR) incorporation, similar to functional CD4+ T cells. Stimulation with a T-cell mitogen, concanavalin A (Con A), also induced the [H-3]TdR incorporation and interleukin-2 receptor (IL-2R) expression in LEC rat CD4+ T cells. Nevertheless, Con A stimulation did not induce IL-2 production by these cells. However, when the stimulation signals were bypassed by ionomycin and phorbol 12-myristate 13-acetate (PMA), IL-2 was normally produced, suggesting that the IL-2 gene and nuclear factors for the IL-2 gene transcription are normal in LEC rats. These results suggest that signals induced by Con A are separated into the one for IL-2 secretion and the other for cell activation including DNA synthesis and IL-2R expression, and that the former signal transduction is blocked in LEC rat CD4+ T cells. Thus, CD4+ T cells in LEC rat LN might provide a good tool for investigating the regulatory mechanisms of IL-2 production.
  • T YAMADA, T AGUI, Y SUZUKI, M SATO, K MATSUMOTO JOURNAL OF BIOLOGICAL CHEMISTRY 268 (12) 8965 -8971 1993年04月 [査読無し][通常論文]
     
    Although ceruloplasmin is known to be a copper-transporting protein, little is known about the biochemical mechanisms of copper incorporation into ceruloplasmin during the biosynthesis. We have examined various levels of ceruloplasmin biosynthesis in the Long-Evans Cinnamon (LEC) rat, which possesses a mutation causing the deficiency in serum ceruloplasmin activity associated with excess hepatic copper accumulation. Southern and Northern blot analyses revealed that the gene and mRNA encoding ceruloplasmin resided normally in LEC rat liver. Western blot analysis showed a normal level of ceruloplasmin in LEC rat serum. Following metabolic labeling of hepatocytes with Cu-64, no radioactive copper was detected in the ceruloplasmin fraction in LEC rat hepatocytes using Sephadex G-75 column chromatography, indicating that copper incorporation into ceruloplasmin is deficient in the LEC rat. Furthermore, LEC rat hepatocytes incubated with Cu-64 also showed a reduction in the efficiency of copper transport from cytosolic to noncytosolic fractions and a reduced copper efflux from the hepatocytes, indicating that LEC rat hepatocytes possess an abnormality in copper metabolism. These results suggest that an abnormality of the copper delivery mechanism causes an inhibition of copper incorporation into the ceruloplasmin molecule in the liver, leading to the deficiency in serum ceruloplasmin activity in the LEC rat. In addition, this abnormality also seems to cause an inhibition of biliary copper excretion. The blocking of these two copper exclusion pathways is thought to lead to excess hepatic copper accumulation in the LEC rat. Thus, the LEC rat should be a good model for studying the biochemical process responsible for copper delivery.
  • T YAMADA, T AGUI, Y SUZUKI, M SATO, K MATSUMOTO JOURNAL OF BIOLOGICAL CHEMISTRY 268 (12) 8965 -8971 1993年04月 [査読無し][通常論文]
     
    Although ceruloplasmin is known to be a copper-transporting protein, little is known about the biochemical mechanisms of copper incorporation into ceruloplasmin during the biosynthesis. We have examined various levels of ceruloplasmin biosynthesis in the Long-Evans Cinnamon (LEC) rat, which possesses a mutation causing the deficiency in serum ceruloplasmin activity associated with excess hepatic copper accumulation. Southern and Northern blot analyses revealed that the gene and mRNA encoding ceruloplasmin resided normally in LEC rat liver. Western blot analysis showed a normal level of ceruloplasmin in LEC rat serum. Following metabolic labeling of hepatocytes with Cu-64, no radioactive copper was detected in the ceruloplasmin fraction in LEC rat hepatocytes using Sephadex G-75 column chromatography, indicating that copper incorporation into ceruloplasmin is deficient in the LEC rat. Furthermore, LEC rat hepatocytes incubated with Cu-64 also showed a reduction in the efficiency of copper transport from cytosolic to noncytosolic fractions and a reduced copper efflux from the hepatocytes, indicating that LEC rat hepatocytes possess an abnormality in copper metabolism. These results suggest that an abnormality of the copper delivery mechanism causes an inhibition of copper incorporation into the ceruloplasmin molecule in the liver, leading to the deficiency in serum ceruloplasmin activity in the LEC rat. In addition, this abnormality also seems to cause an inhibition of biliary copper excretion. The blocking of these two copper exclusion pathways is thought to lead to excess hepatic copper accumulation in the LEC rat. Thus, the LEC rat should be a good model for studying the biochemical process responsible for copper delivery.
  • Maturational arrest from CD4+8+ to CD4+8- thymocytes is caused by the bone marrow-derived cells in LEC mutant rate.
    Immunol. Lett. 38 145 -152 1993年 [査読無し][通常論文]
  • Y MURAMATSU, T YAMADA, T AGUI, J YAMADA, T SERIKAWA, K MATSUMOTO CYTOGENETICS AND CELL GENETICS 63 (3) 141 -143 1993年 [査読無し][通常論文]
     
    Chromosomal assignments of genes for rat glutathione S-transferase Yb1 (GSTA3) and Yb2 (GSTA4) subunits were performed by Southern blot analyses of somatic cell hybrid DNAs. Both GSTA3 and GSTA4 were assigned to rat chromosome 2.
  • 山田 宜永, Moralejo D, 安居院 高志, 松本 耕三 J. Vet. Med. Sci. 55 (3) 491 -492 1993年 [査読無し][通常論文]
  • YAMADA T, MORALEJO D, TSUCHIYA K, AGUI T, MATSUMOTO K J. Vet. Med. Sci. 55 (4) 673 -675 1993年 [査読無し][通常論文]
  • Maturational arrest from CD4+8+ to CD4+8- thymocytes is caused by the bone marrow-derived cells in LEC mutant rate.
    Immunol. Lett. 38 145 -152 1993年 [査読無し][通常論文]
  • Y MURAMATSU, T YAMADA, T AGUI, J YAMADA, T SERIKAWA, K MATSUMOTO CYTOGENETICS AND CELL GENETICS 63 (3) 141 -143 1993年 [査読無し][通常論文]
     
    Chromosomal assignments of genes for rat glutathione S-transferase Yb1 (GSTA3) and Yb2 (GSTA4) subunits were performed by Southern blot analyses of somatic cell hybrid DNAs. Both GSTA3 and GSTA4 were assigned to rat chromosome 2.
  • Takahisa YAMADA, Daniel MORAREJO, Takashi AGUI, Kozo MATSUMOTO J. Vet. Med. Sci. 55 (3) 491 -492 1993年 [査読無し][通常論文]
  • J. Vet. Med. Sci. 55 (4) 673 -675 1993年 [査読無し][通常論文]
  • T YAMADA, T AGUI, K MATSUMOTO BIOCHEMISTRY INTERNATIONAL 27 (4) 671 -678 1992年08月 [査読無し][通常論文]
  • T YAMADA, T AGUI, K MATSUMOTO BIOCHEMISTRY INTERNATIONAL 27 (4) 671 -678 1992年08月 [査読無し][通常論文]
  • T YAMADA, K SOGAWA, Y SUZUKI, K IZUMI, T AGUI, K MATSUMOTO RESEARCH COMMUNICATIONS IN CHEMICAL PATHOLOGY AND PHARMACOLOGY 77 (1) 121 -124 1992年07月 [査読無し][通常論文]
     
    Long-Evans Cinnamon (LEC) mutant rat, which spontaneously develops a chronically necrotizing hepatic injury at 4-5 months age, exhibits an excess hepatic copper accumulation. The hepatic injury was completely correlated to the excess hepatic copper accumulation in backcross progenies, supporting the previous hypothesis that the copper cytotoxicity causes the hepatic injury in LEC rat liver. The levels of the lipid peroxidation in symptomatic LEC rats at 4 months of age were significantly higher than those of age-matched asymptomatic LEC and normal rats. These results suggest that excessively accumulated copper provokes hepatic injury through initiating the lipid peroxidation.
  • T YAMADA, Y MURAMATSU, T AGUI, K MATSUMOTO BIOCHEMISTRY INTERNATIONAL 27 (2) 243 -249 1992年07月 [査読無し][通常論文]
  • T YAMADA, K SOGAWA, Y SUZUKI, K IZUMI, T AGUI, K MATSUMOTO RESEARCH COMMUNICATIONS IN CHEMICAL PATHOLOGY AND PHARMACOLOGY 77 (1) 121 -124 1992年07月 [査読無し][通常論文]
     
    Long-Evans Cinnamon (LEC) mutant rat, which spontaneously develops a chronically necrotizing hepatic injury at 4-5 months age, exhibits an excess hepatic copper accumulation. The hepatic injury was completely correlated to the excess hepatic copper accumulation in backcross progenies, supporting the previous hypothesis that the copper cytotoxicity causes the hepatic injury in LEC rat liver. The levels of the lipid peroxidation in symptomatic LEC rats at 4 months of age were significantly higher than those of age-matched asymptomatic LEC and normal rats. These results suggest that excessively accumulated copper provokes hepatic injury through initiating the lipid peroxidation.
  • T YAMADA, Y MURAMATSU, T AGUI, K MATSUMOTO BIOCHEMISTRY INTERNATIONAL 27 (2) 243 -249 1992年07月 [査読無し][通常論文]
  • T YAMADA, Y SUZUKI, T AGUI, K MATSUMOTO BIOCHIMICA ET BIOPHYSICA ACTA 1131 (2) 188 -191 1992年06月 [査読無し][通常論文]
     
    The mechanism of the metallothionein (MT) gene expression was investigated in a mutant rat, LEC, which exhibits an abnormal accumulation of copper in hepatocytes. The levels of MT mRNA were extremely high and correlated with the hepatic copper concentrations in LEC rat liver. Gel retardation assays in nuclear extracts from LEC rat liver showed an increase in the copper-dependent binding proteins, which bind to the metal responsive element (MRE) of the MT gene. These results suggest that the high intracellular copper accumulation results in the elevation of the MT gene expression through increasing a putative trans-activating factor in LEC rat.
  • T YAMADA, Y SUZUKI, T AGUI, K MATSUMOTO BIOCHIMICA ET BIOPHYSICA ACTA 1131 (2) 188 -191 1992年06月 [査読無し][通常論文]
     
    The mechanism of the metallothionein (MT) gene expression was investigated in a mutant rat, LEC, which exhibits an abnormal accumulation of copper in hepatocytes. The levels of MT mRNA were extremely high and correlated with the hepatic copper concentrations in LEC rat liver. Gel retardation assays in nuclear extracts from LEC rat liver showed an increase in the copper-dependent binding proteins, which bind to the metal responsive element (MRE) of the MT gene. These results suggest that the high intracellular copper accumulation results in the elevation of the MT gene expression through increasing a putative trans-activating factor in LEC rat.
  • T AGUI, T YAMADA, G LEGROS, T NAKAJIMA, M CLARK, C PESCHEL, K MATSUMOTO ENDOCRINOLOGY 130 (5) 2487 -2494 1992年05月 [査読無し][通常論文]
     
    Atrial natriuretic peptide (ANP) receptors were identified on both murine bone marrow-derived stromal cell lines A-3 and ALC and primary cultured cells using [I-125]ANP binding assays and Northern blot analyses. The binding of [I-125] ANP to the stromal cells was rapid, saturable, and of high affinity. The dissociation constants between ANP and its receptors on these cells showed no difference among cell types, while maximal binding capacity values were different among cell types. Competitive inhibition of [I-125]ANP binding with C-atrial natriuretic factor, specific for ANP clearance receptor (ANPR-C), revealed that most of [I-125]ANP-binding sites corresponded to ANPR-C. Northern blotting data corroborated that bone marrow-derived stromal cells expressed ANPR-C. However, in ALC cells, ANP biological receptors (either ANPR-A or ANPR-B), the mol wt of which is approximately 130K, were detected, and cGMP was accumulated after stimulation with ANP. On the other hand, in another stromal cell clone, A-3 cells, the expression of biological receptor was not detected in the affinity cross-linking and competitive inhibition experiments using [I-125]ANP. However, A-3 cells accumulated cGMP by responding to ANPR-B-specific ligand, C-type natriuretic peptide. These results suggest that ALC cells equally express ANPR-A and ANPR-B, while A-3 cells express ANPR-B dominantly. Although the physiological roles of these receptors in the bone marrow is still not resolved, ANP is expected to play a role in the regulation of stromal cell functions in bone marrow.
  • T AGUI, T YAMADA, G LEGROS, T NAKAJIMA, M CLARK, C PESCHEL, K MATSUMOTO ENDOCRINOLOGY 130 (5) 2487 -2494 1992年05月 [査読無し][通常論文]
     
    Atrial natriuretic peptide (ANP) receptors were identified on both murine bone marrow-derived stromal cell lines A-3 and ALC and primary cultured cells using [I-125]ANP binding assays and Northern blot analyses. The binding of [I-125] ANP to the stromal cells was rapid, saturable, and of high affinity. The dissociation constants between ANP and its receptors on these cells showed no difference among cell types, while maximal binding capacity values were different among cell types. Competitive inhibition of [I-125]ANP binding with C-atrial natriuretic factor, specific for ANP clearance receptor (ANPR-C), revealed that most of [I-125]ANP-binding sites corresponded to ANPR-C. Northern blotting data corroborated that bone marrow-derived stromal cells expressed ANPR-C. However, in ALC cells, ANP biological receptors (either ANPR-A or ANPR-B), the mol wt of which is approximately 130K, were detected, and cGMP was accumulated after stimulation with ANP. On the other hand, in another stromal cell clone, A-3 cells, the expression of biological receptor was not detected in the affinity cross-linking and competitive inhibition experiments using [I-125]ANP. However, A-3 cells accumulated cGMP by responding to ANPR-B-specific ligand, C-type natriuretic peptide. These results suggest that ALC cells equally express ANPR-A and ANPR-B, while A-3 cells express ANPR-B dominantly. Although the physiological roles of these receptors in the bone marrow is still not resolved, ANP is expected to play a role in the regulation of stromal cell functions in bone marrow.
  • T YAMADA, K IZUMI, Y SUZUKI, T AGUI, K MATSUMOTO RESEARCH COMMUNICATIONS IN CHEMICAL PATHOLOGY AND PHARMACOLOGY 76 (1) 113 -116 1992年04月 [査読無し][通常論文]
     
    Long-Evans Cinnamon ( LEC ) rat, an animal model of Wilson's disease, that develops a necrotizing hepatic injury with an abnormally high hepatic copper accumulation exhibits an altered expression of glutathione S-transferase (GST) subunits, that is, a low percentage of the Ya and a high percentage of the Yc subunit expression in males. The altered expression of GST subunits and the abnormal copper accumulation in liver were found to be completely correlated in male LEC mutant rat liver, suggesting that the copper toxicity caused by the anomaly of copper metabolism in LEC rat liver leads to the altered expression of GST subunits.
  • T YAMADA, K IZUMI, Y SUZUKI, T AGUI, K MATSUMOTO RESEARCH COMMUNICATIONS IN CHEMICAL PATHOLOGY AND PHARMACOLOGY 76 (1) 113 -116 1992年04月 [査読無し][通常論文]
     
    Long-Evans Cinnamon ( LEC ) rat, an animal model of Wilson's disease, that develops a necrotizing hepatic injury with an abnormally high hepatic copper accumulation exhibits an altered expression of glutathione S-transferase (GST) subunits, that is, a low percentage of the Ya and a high percentage of the Yc subunit expression in males. The altered expression of GST subunits and the abnormal copper accumulation in liver were found to be completely correlated in male LEC mutant rat liver, suggesting that the copper toxicity caused by the anomaly of copper metabolism in LEC rat liver leads to the altered expression of GST subunits.
  • T YAMADA, Y MURAMATSU, M YASUE, T AGUI, J YAMADA, K MATSUMOTO CYTOGENETICS AND CELL GENETICS 61 (2) 125 -127 1992年 [査読無し][通常論文]
     
    Chromosomal assignments of genes for rat glutathione S-transferase Ya (GSTA1) and Yc subunits (GSTA2) were performed by Southern blot analyses of somatic cell hybrid DNAs. GSTA 1 and GSTA2 were assigned to rat chromosomes 8 and 9, respectively.
  • T YAMADA, Y MURAMATSU, M YASUE, T AGUI, J YAMADA, K MATSUMOTO CYTOGENETICS AND CELL GENETICS 61 (2) 125 -127 1992年 [査読無し][通常論文]
     
    Chromosomal assignments of genes for rat glutathione S-transferase Ya (GSTA1) and Yc subunits (GSTA2) were performed by Southern blot analyses of somatic cell hybrid DNAs. GSTA 1 and GSTA2 were assigned to rat chromosomes 8 and 9, respectively.
  • T YAMADA, T NATORI, K IZUMI, T SAKAI, T AGUI, K MATSUMOTO IMMUNOGENETICS 33 (3) 216 -219 1991年03月 [査読無し][通常論文]
  • T YAMADA, T NATORI, K IZUMI, T SAKAI, T AGUI, K MATSUMOTO IMMUNOGENETICS 33 (3) 216 -219 1991年03月 [査読無し][通常論文]
  • AGUI T, SAKAI T, HIMENO K, MATSUMOTO K Eur. J. Immunol. 21 (9) 2277 -2280 1991年 [査読無し][通常論文]
  • AGUI T, SAKAI T, MATSUMOTO K Eur. J. Immunol. 21 (10) 2537 -2541 1991年 [査読無し][通常論文]
  • Ecto-ATPase activity in cytolytic T-Iymphocytes: Protection from the cytolytic effects of extracellular ATP.
    J. Biol. Chem. 265 334 -340 1990年 [査読無し][通常論文]
  • AGUI T, OKA M, YAMADA T, SAKAI T, IZUMI K, ISHIDA Y, HIMENO K, MATSUMOTO K J. Exp. Med. 172 (6) 1615 -1624 1990年 [査読無し][通常論文]
  • Ecto-ATPase activity in cytolytic T-Iymphocytes: Protection from the cytolytic effects of extracellular ATP.
    J. Biol. Chem. 265 334 -340 1990年 [査読無し][通常論文]
  • Direct demonstration of guanine nucleotides sensitive receptors for vasoactive intestinal peptide in the anterior lobe of the rat pituitary gland.
    Peptides 11 609 -611 1990年 [査読無し][通常論文]
  • J. Exp. Med. 172 (6) 1615 -1624 1990年 [査読無し][通常論文]
  • M MUNEMURA, T AGUI, DR SIBLEY ENDOCRINOLOGY 124 (1) 346 -355 1989年01月 [査読無し][通常論文]
  • AGUI T, KURIHARA M, SAAVEDRA J M Eur. J. Pharmacol. 162 (2) 301 -307 1989年 [査読無し][通常論文]
  • M MUNEMURA, T AGUI, DR SIBLEY ENDOCRINOLOGY 124 (1) 346 -355 1989年01月 [査読無し][通常論文]
  • Eur. J. Pharmacol. 162 (2) 301 -307 1989年 [査読無し][通常論文]
  • T AGUI, TN CHASE, JW KEBABIAN BRAIN RESEARCH 452 (1-2) 49 -56 1988年06月 [査読無し][通常論文]
  • T AGUI, TN CHASE, JW KEBABIAN BRAIN RESEARCH 452 (1-2) 49 -56 1988年06月 [査読無し][通常論文]
  • T AGUI, N AMLAIKY, MG CARON, JW KEBABIAN JOURNAL OF BIOCHEMISTRY 103 (3) 436 -441 1988年03月 [査読無し][通常論文]
  • T AGUI, N AMLAIKY, MG CARON, JW KEBABIAN JOURNAL OF BIOCHEMISTRY 103 (3) 436 -441 1988年03月 [査読無し][通常論文]
  • Binding of [125I]-N-(p-aminophenethyl)spiroperidol to the D-2 dopamine receptor in the neurointermediate lobe of the rat pituitary gland: A thermodynamic study.
    Mol. Pharmacol. 32 163 -169 1988年 [査読無し][通常論文]
  • Binding of [125I]-N-(p-aminophenethyl)spiroperidol to the D-2 dopamine receptor in the neurointermediate lobe of the rat pituitary gland: A thermodynamic study.
    Mol. Pharmacol. 32 163 -169 1988年 [査読無し][通常論文]
  • 125I-Iodinated benzazepines bind to melanin: Implications for the noninvasive localization of pigmented melanomas.
    Int. J. Rad. Appl. Instrum. B. 14 133 -141 1987年 [査読無し][通常論文]
  • 125I-Iodinated benzazepines bind to melanin: Implications for the noninvasive localization of pigmented melanomas.
    Int. J. Rad. Appl. Instrum. B. 14 133 -141 1987年 [査読無し][通常論文]
  • JW KEBABIAN, T AGUI, JC VANOENE, K SHIGEMATSU, JM SAAVEDRA TRENDS IN PHARMACOLOGICAL SCIENCES 7 (3) 96 -99 1986年03月 [査読無し][通常論文]
  • JW KEBABIAN, T AGUI, JC VANOENE, K SHIGEMATSU, JM SAAVEDRA TRENDS IN PHARMACOLOGICAL SCIENCES 7 (3) 96 -99 1986年03月 [査読無し][通常論文]
  • K MATSUMOTO, T NATORI, T AGUI, S TSUTIMOTO, A MATSUHASHI, DL GASSER BIOCHEMICAL GENETICS 24 (1-2) 93 -102 1986年02月 [査読無し][通常論文]
  • K MATSUMOTO, T NATORI, T AGUI, S TSUTIMOTO, A MATSUHASHI, DL GASSER BIOCHEMICAL GENETICS 24 (1-2) 93 -102 1986年02月 [査読無し][通常論文]
  • The structural relation between the antigenic determinants to monoclonal antibodies and binding sites to rat brain synaptosomes and GTlb ganglioside in Clostridium botulinum type C neurotoxin.
    J. Biochem. 97 213 -218 1985年 [査読無し][通常論文]
  • The structural relation between the antigenic determinants to monoclonal antibodies and binding sites to rat brain synaptosomes and GTlb ganglioside in Clostridium botulinum type C neurotoxin.
    J. Biochem. 97 213 -218 1985年 [査読無し][通常論文]
  • T AGUI, B SYUTO, K OGUMA, H IIDA, S KUBO JOURNAL OF BIOCHEMISTRY 94 (2) 521 -527 1983年 [査読無し][通常論文]
  • T AGUI, B SYUTO, K OGUMA, H IIDA, S KUBO JOURNAL OF BIOCHEMISTRY 94 (2) 521 -527 1983年 [査読無し][通常論文]
  • Four different monoclonal antibodies against type C1 toxin of Clostridium botulinum.
    Infect. Immun. 38 14 -20 1982年 [査読無し][通常論文]
  • Four different monoclonal antibodies against type C1 toxin of Clostridium botulinum.
    Infect. Immun. 38 14 -20 1982年 [査読無し][通常論文]
  • K OGUMA, B SYUTO, T AGUI, H IIDA, S KUBO INFECTION AND IMMUNITY 34 (2) 382 -388 1981年 [査読無し][通常論文]
  • K OGUMA, B SYUTO, T AGUI, H IIDA, S KUBO INFECTION AND IMMUNITY 34 (2) 382 -388 1981年 [査読無し][通常論文]

特許

  • マウス肝炎ウイルス由来ポリペプチドおよび/またはセンダイウイルス由来ポリペプチド、これらを用いたマウス肝炎ウイルス感染および/またはセンダイウイ ルス感染検査キット、ならびにマウス肝炎ウイルス感染および/またはセンダイウイルス感染の検出方法
    PCT/JP2010/057188
  • マウス 肝炎ウイルス由来ポリペプチドおよびこれを用いたマウス肝炎ウイルス感染検査キットならびにマウス肝炎ウイルス感染の検出方法
    特願2009- 104906号
  • センダ イウイルス由来ポリペプチドおよびこれを用いたセンダイウイルス感染検査キットならびにセンダイウイルス感染の検出方法
    特願2009-104905号
  • エリスロポエチン徐放製剤およびその作製方法
    特願2007-33476号

共同研究・競争的資金等の研究課題

  • 各種ミュータントマウス・ラットのゲノム解析 マウス・ラットの感染症抵抗遺伝子の解析
  • Genetic analysis of mutant mice and rats. Genetic analysis of resistance to infections in mice and rats.

教育活動情報

主要な担当授業

  • 研究倫理演習
    開講年度 : 2018年
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • 生命環境倫理学
    開講年度 : 2018年
    課程区分 : 修士課程
    開講学部 : 農学院
    キーワード : 科学研究、科学技術、科学技術コミュニケーション、リスクコミュニケーション、動物実験、研究者倫理、環境倫理、倫理的消費(エシカル消費)、GAP、アニマルウェルフェア、原子力災害、再生可能エネルギー、グローバリゼーション
  • 人獣共通感染症対策専門特論
    開講年度 : 2018年
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • 環境と人間
    開講年度 : 2018年
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 産業動物、伴侶動物、実験動物、動物実験、展示動物、野生動物、動物愛護法、鳥獣保護法、クローン動物、遺伝子組換え動物、寄生虫、人獣共通感染症、脂肪細胞
  • 獣医科学特別研究
    開講年度 : 2018年
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • 実験動物疾病学
    開講年度 : 2018年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 実験動物の微生物コントロール、実験動物の感染症、モデル動物、動物実験倫理、動物実験関連法規等、動物実験技術、実験動物医学
  • 人獣共通感染症対策専門特論
    開講年度 : 2018年
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • 獣医遺伝学
    開講年度 : 2018年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : メンデルの遺伝の法則、連鎖と組換え、連鎖解析、QTL解析、近交系、コンジェニック系、コアイソジェニック系、ミュータント系、クローズドコロニー、被毛色の遺伝、遺伝モニタリング
  • 獣医科学特論演習
    開講年度 : 2018年
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • 微生物学
    開講年度 : 2018年
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 細菌、ウイルス、グラム陽性菌、グラム陰性菌、抗酸性菌、感染症、ワクチン、プリオン、寄生虫、原虫、マイコプラズマ、クラミジア、スピロヘータ、真菌
  • 獣医科学基礎科目B 動物実験倫理特論
    開講年度 : 2018年
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • 実験動物学実習
    開講年度 : 2018年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 実験動物学、微生物的モニタリング、遺伝学的モニタリング 遺伝学、発生工学
  • 獣医科学特別研究
    開講年度 : 2018年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 獣医科学特論演習
    開講年度 : 2018年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 研究倫理演習
    開講年度 : 2018年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 先端獣医科学科目 実験動物学特論
    開講年度 : 2018年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 実験動物医学演習
    開講年度 : 2018年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 研究・臨床セミナー
    開講年度 : 2018年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • アドバンスト演習
    開講年度 : 2018年
    課程区分 : 学士課程
    開講学部 : 獣医学部

大学運営

委員歴

  • 2009年   日本実験動物学会   評議員   日本実験動物学会
  • 2007年   日本動物実験代替法学会   評議員   日本動物実験代替法学会
  • 2007年   日本獣医学会   理事   日本獣医学会


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