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1995 Fiscal Year Final Research Report Summary

Establishment of murine strains separately with various autoimmune diseases

Research Project

Project/Area Number 05558102
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Laboratory animal science
Research InstitutionTohoku University

Principal Investigator

NOSE Masato  Tohoku Univ. Sch. Med. Pathol., Associate Prof., 医学部, 助教授 (70030913)

Co-Investigator(Kenkyū-buntansha) KATO Hideki  Central Inst. for Exp. Animals, Chief, 室長 (30142053)
YAMAMOTO Tokuo  Tohoku Univ. Gene Res. Center, Prof., 遺伝子実験施設, 教授 (30192412)
NISHIMURA Masahiko  Hamamatu Univ., Exp. Animals, Ass. Prof., 動物実験施設, 助教授 (20073661)
Project Period (FY) 1993 – 1995
KeywordsCollagen disease / Vasculitis / Arthritis / Glomerulonephritis / Fas / Apoptosis / Background gene / Autoantibody
Research Abstract

1. MRL/lpr, but not C3H/lpr mice, develop autoimmune diseases coincidentally involving vasculitis, arthritis and glomerulonephritis (GN). Two novel congenic strains of mice, which separately developed severe vasculitis and arthritis, respectively, were established from the MRL/lpr and C3H/lpr strains, indicating that these diseases are under the control of suppressor and enhancer genes. 2. By using MRL/lpr x (MRL/lpr x C3H / lpr) F1 mice, we analyzed the linkage of vasculitis with microsatellite makers to find out the corresponding background gene locus. 3. We obtained nephritogenic antibody-producing B cell clones from MRL/lpr mice and were succeeded in cloning of their germline VH genes. These genes were localized also in normal strains of mice. The background genes for GN,thus, are not immunoglobulin genes by themselves and these contribute to the inducing mechanisms of nephritogenic antibodies. 4. Eta-1/Op induces macrophage-and polyclonal B cell-activation. We obseved allelic difference in the Eta-1 gene transcript between MRL and C3H strains, which was enough to induce a functional difference. This can be one of disease-sensitive genes for autoimmune diseases. 5. We newly astablished an MRL strain of mice bearing Fas ligand mutant gene, gld, which developed autoimmune diseases as well as MRL/ipr mice. The treatment with anti-Fas antibodies suppressed and ameliorated the diseases, indicating that the diseases are due to the deficit in Fas/FasL interaction. 6. Transfer of the interferon regulatory factor-1 gene, IRF-1, to MRL/lpr mice induced the selective suppression of autoimmune diseases in MRL/lpr mice. This indicates that some autoimmune diseases, but not all, are under the control of the background genes regulatable by IRF-1.

  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Takahashi, S.: "Cloning and cDNA sequente analysis of nephritogenic monoclonal antibodies derived from an MRL/lpr mouse" Mol. Immunol.30. 177-182 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fossati, L.: "An MRL/MpJ-lpr/lpr substrain with a limited expansion of lpr double negative Tcells and a reduced autoimmune" Int. Immunol.5. 525-532 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Itoh, J.: "Induction of different types of glomerulonephritis by monoclonal antibodies derived from an MRL/lpr mouse" Am. J. Pathol.143. 1436-1443 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 能勢眞人: "ループル腎炎原性抗体の分子病理学" 細胞. 26. 32-36 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanno, H.: "Immune complex-degradation ability of macrophages in MRL/Mp-lpr/lpr lupus mice-" Clin. Exp. Immunol.95. 115-121 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 伊藤美津子: "難治性血管炎の動物モデル" 日本臨床. 52. 1982-1986 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ono, M.: "Sequence analysis of the germline VH gene corresponding to a nephritogenic antibody in MRL/lpr mice" Clin. Exp. Immunol.100. 284-290 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ono, M.: "A novel germline VH gene encoding a murine nephritopenic auto antibody" Immunogenetics. 42. 426-427 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ono, M.: "Allelic difference in the nucleotide sequence of the Eta-1/Op gene transcript" Mol. Immunol.32. 447-448 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 能勢眞人: "膠原病における血管障害-その病理像と発症機序の多様性-" 実験医学. 13. 271-279 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nose, M.: "Vascular lesions in mice with a deficit in Fas-mediated apoptosis and their transfer" Int. J. Cardiol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nose, M.(分担): "Intractable Vasculitis Syndromes" Hokkaido Univ. Press, 284 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 能勢眞人(分担): "現代病理学大系(第6巻,免疫)" 中山書店, 398 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi, S.et al: "Cloning and cDNA sequence analysis of nephritogenic monoclonal antibodies derived from an MRL/ipr mice" Mol. Immunol. 30. 177-182 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fossati, L.et al: "An MRL/MpJ-lpr/lpr substrain with a limited expansion of lpr double negative T cells and a reduced autoimmune syndrome" Int. Immunol. 5. 525-532 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Heyman, B.et al: "Antibody feedback regulation in MRL/lpr mice." J.Autoimmunity. 6. 437-448 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Itoh, J.et al: "Induction of different types of glomerulonephritis by monoclonal antibodies derived from MRL/lpr lupus mouse." Am. J.Pathol. 143. 1436-1443 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nose, M.: "Genetic basis of vasculitis in lupus mice." Intractable Vasculitis Syndromes (T.Tanabe, ed.), Hokkaido Univ. Press.145-153 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanno, H.et al.: "Immune complex-degradation ability of macrophages in MRL/Mp-lpr/lpr lupus mice and its regulation by cytokines" Clin. Exp. Immunol. 95. 115-121 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Itoh, J.et al.: "Nephritogenic antibodies in MRL/lpr lupus mice : Molecular characteristics in pathological and genetic aspects" Tohoku J.Exp. Med. 173. 65-74 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ono, M.et al.: "Sequence analysis of the germline VH gene corresponding to a nephritogenic antibody in MRL/lpr mice." Clin. Exp. Immunol. 100. 284-290 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ono, M.et al.: "A novel germline VH gene encoding a murine nephritogenic autoantibody." Immunogenetics. 42. 426-427 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ono, M.et al.: "Alleclic difference in the nucleotide sequence of the Eta-1/Op gene transcript." Mol. Immunol. 32. 447-448 (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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