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1996 Fiscal Year Final Research Report Summary

Joint study of antigen presenting activity in NOD mice

Research Project

Project/Area Number 08044322
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionTokai University

Principal Investigator

HABU Sonoko  Tokai Univ.Sch.Medicine, Professor, 医学部, 教授 (30051618)

Co-Investigator(Kenkyū-buntansha) SIMPSON Elizabeth  MRC Clinical Science Center Royal Postgraduate Medical School, Professor, Professor
SATO Takehito  Tokai Univ.Sch.Medicine, Lecturer, 医学部, 助手 (50235363)
Project Period (FY) 1996
KeywordsNOD mouse / Ii gene / Idd3 / IL-2 / type C endogenous retrovirus
Research Abstract

The NOD mice have been used as a IDDM model for studying multigenic diseases because at least 16 different loci, named Idd, have been reported. However, their substantial genes are remained unclear except Idd1 which is linked to MHC class II.In this academic year, we explored the related genes for immune responsiveness including antigen presenting activity of NOD mice among Idds or others, and obtained the followings. 1) In use of two congenic staine for Idd 3 and Idd4 by introducing chromosomal segments from MSM stain into the genetic background of NOD mice, we found that insulitis is clear in NOD-Idd4 but not in NOD-Idd3, and that a region responsible for severe insulitis is located in the Idd3 region between D3MIT169 and D3MIT181 including IL-2 gene. In fact, the level of IL-2 production from T cells of MSM was higher than that of NOD by crosslinking CD3 in vitro. thus, it is strongly suggested that IL-2 is a plausible candidate gene of Idd3.2) Since retrovirus may be integrated into genom to induce mutation of certain genes, we examined particular insertions of Env gene fragment of C-Type retrovirus and found a Env insertion into 18 chromosome of NOD mice in which the insertion was mapped within 1cM of Ii gene responsible to antigen presentation. However, we have not obtained a direct evidence that Env insertion contributes for alteration of Ii gene structure or its function. In putative conclusion from these data, the lower Ii gene expression which we obtained in NOD mice may come from the low production of IL-2 whose gene is located in Idd3. Further analysis is required.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] T.Nishimura,K.Santa,T.Yahata,N.Sato,A.Ohta,Y.Ohmi,et al.: "Involvement of IL-4 producing Vβ8.2^+CD^+CD62L^-CD45RB^- T cells in Non-MHC gene controlled predisposition toward skewing into T helper type-^2 immunity in BALB/c mice^1" J.Immunol.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Tanaka,A.Takahashi,K.Watanabe,K.Takayama,et al.: "A pivotal role of IL-2 in Thl-dependent mouse liver injury." Int.Immunol.6. 569-576 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nozaki,K.Hozumi,T.Nishimura and S.Habu: "Regulation of NK activity by the adiministration of bromocriptine in haloperidol treated mice." Brain,Behavior,and Immunity. 10. 17-26 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Miyakawa,T.Nishimura,Y.Ueyama,K.Miyake,et al.: "Cell adhesion via murine α4 human β1 integrin chimera on transfected K562 cells to endotherllal cells." Exp.Cell Res.226. 75-79 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Hozumi,A.Kobori,T.Sato,T.Nishimura and S.Habu: "Transcription and demethylation of TCR β gene initiate prior to the gene rearrangeme in c-kit^+ thymocytes with CD3 expression : evidence of T-cell commitment in the thymus." Int.Immunol.10. 1473-1481 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Sato,K.Hozumi,K.Kishihara,Y.Kametani,C.Sato,et al.: "Evidence for down-regulation of highly expressed T cell receptor by CD4 and CD45 on non-selected CD4^+CD8^+ thymocytes." Int.Immunol.10. 1529-1536 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Tanaka: "A pivotal role of IL-12 in Th1-dependent mouse liver injury." Int.Immunol. 6. 569-576 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nozaki: "Regulation of NK activity by the adiministration of bromocriptine in haloperidol treated mice." Brain.Behavior, and Immunity. 10. 17-26 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Miyakawa: "Cell adhesion via murine alpha4 human beta1 integrin chimera on transfected K562 cells to endotherllal cells." Exp.Cell Res.226. 75-79 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hozumi: "Transcription and demethylation of TCR beta gene initiate prior to the gene rearrangement in c-kit^+ thymocytes with CD3 expression : evidence of T-cell commitment in the thymus." Int.Immunol. 8. 1473-1481 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Sato: "Evidence for down-regulation of highly expressed T cell receptor by CD4 and CD45 on non-selected CD4^+CD8^+ thymocytes" Int.Immunol.8. 1529-1536 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Nishimura: "Involvement of IL-4 producing Vbeta8.2^+CD^+ CD62L^-CD45RB^- T cells in Non-MHC gene controlled predisposition toward skewing into T helper type^<-2> immunity in BALB/c mice^1" J.Immunol. (in press). (1997)

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

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Published: 1999-03-09  

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