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1996 Fiscal Year Final Research Report Summary

Prevention of type 1 diabetes mellitus by the regulation of pancreas-specific retrovirus expression using the transplacental gene transfer method.

Research Project

Project/Area Number 08457265
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionOsaka University

Principal Investigator

NAKAJIMA Hiromu  Osaka University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (50252680)

Co-Investigator(Kenkyū-buntansha) ASAKAWA Hideki  Osaka University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (60283785)
MIYAGAWA Jun-ichiro  Osaka University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (00127721)
NAMBA Mitsuyoshi  Osaka University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (00183533)
HANAFUSA Toshiaki  Osaka University, Faculty of Medicine, Lecturer, 医学部, 講師 (60164886)
Project Period (FY) 1996
Keywordstype 1 diabetes mellitus / retrovirus / positional cloning / disease susceptible gene / viral infection / pancreas beta-cell destruction / NOD mouse / gene delivery method
Research Abstract

The non-obese diabetic (NOD) mouse develop type I diabetes mellitus characterized by a massive lymphocytic infiltration into the pancreatic islets. A viral role has been suggested in the pathogenesis of this type of diabetes mellitus. We report here the cloning of retrovirus cDNA whose expression was considered to be specific to the pancreas of the NOD mouse. The provirus differs in sequence from all other published type C retrovirsues. The virus has a relatively well conserved gag region, and a truncated pol region with a large deletion. Almost all env region were deleted, and a trace of the sequence motif was included 3'to the pol region. These structural features are characteristic of replication defective viruses. Viral mRNA expression level was highest in 4-week-old NOD mice. The onset of insulitis also occurs from 4 weeks of age in the NOD mouse, thus suggesting a role for the virus in the pathogenesis of diabetes in this animal model.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] K.Yamagata, H.Nakajima, et al.: "Dominant TCR α-chain clonotypes and interferon-γare cxpressed in the pancreas of patients with recent-onset insulin-dependent diabetes mellitus." Diabetes Res.Clin.Practice. 34(9). 37-46 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Iwahashi, T, H.Nakajima, et al.: "Cytokine-induced apoptotic cell death in a mouse pancreatic beta cell line:inhibition by Bcl-2." Diabetologia. 39(5). 530-536 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Imagawa, H.Nakajima, et al.: "High prevalence of antibodies to glutamic acid decarboxylase in comparison to islet ccll antibodies in patients with long-standing insulin-depcndent diabetes mellitus." Res.Commun.Mol.Pathol.Pharmacol.92(1). 43-52 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Imagawa, H.Nakajima, et al.: "Islet infiltrating T-lymphocytee from insulin-dependent diabetic patients express CD80(B7-1)and CD86(B7-2)." J.Autoimmunity. 9(3). 391-396 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Hanafusa, H.Nakajima, et al.: "Role of retrovirus for the pathogenesis of diabetes in the NOD mouse." Lessons from Animal Diabetes. E.Shafrir,Y.Kanazawa,eds.,Smith-Gordon,London,. 77-82 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nakajima, et al.: "Hepatocyle unclear factor-4α gene mutations in Japanese non-insulin dependent diabetes mellitus(NIDDM) patients." Res.Commun.Mol.Pathol.Pharmacol.94(3). 327-330 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Yamagata, H.Nakajima, K.Tomita, N.Ito, J.Miyagawa, T.Hamaguchi, M.Namba, S.Tamura, S.Kawata, N.Kono, M.Kuwajima, T.Noguchi, T.Hanafusa, Y.Matsuzawa: "Dominant TCR alpha-chain clonotypes and interferon-gamma are expressed in the pancreas of patients with recent-onset insulin-dependent diabetes mellitus." Diabetes Res.Clin.Practice. 34 (9). 37-46 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Iwahashi, T.Hanafusa, Y.Eguchi, H.Nakajima, J.Miyagawa, N.Itoh, K.Tomita, M.Namba, M.Kuwajima, T.Noguchi, Y.Tsujimoto, Y.Matsuzawa: "Cytokine-induced apoptotic cell death in a mouse pancreatic beta cell line : inhibition by Bc1-2." Diabetologia. 39 (5). 530-536 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Imagawa, N.Ito, T.Hanafusa, H.Katsura, A.Yamaguchi, A.Takeda, H.Nakajima, J.Miyagawa, M.Namba, M.Kuwajima, Y.Matsuzawa: "High prevalence of antibodies to glutamic acid decarboxylase in comparison to islet cell antibodies in patients with long-standing insulin-dependent diabetes mellitus." Res.Commun.Mol.Pathol.Pharmacol.92 (1). 43-52 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Imagawa, T.Hanafusa, N.Ito, J.Miyagawa, S.Tamura, S.Kawata, M.Kuwajima, H.Nakajima, M.Namba, Y.Matsuzawa, D.M.Harlan: "Islet infiltrating T-lymphocytee from insulin-dependent diabetic patients express CD80 (B7-1) and CD86 (B7-2)." J.Autoimmunity. 9 (3). 391-396 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Hanafusa, K.Tomita, H.Nakajima, C.Nakagawa, J.Miyagawa, M.Kuwajima, S.Tarui, Y.Matsuzawa: "Role of retrovirus for the pathogenesis of diabetes in the NOD mouse." Lessons from Animal Diabetes. E.Shafrir, Y.Kanazawa, eds., Smith-Gordon, London. 77-82 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nakajima, I.Yoshiuchi, T.Hamaguchi, K.Tomita, T.Yamasaki, K.Iizuka, K.Okita, M.Moriwaki, A.Ono, T.Oue, Y.Horikawa, R.Shingu, J.Miyagawa, M.Namba, T.Hanafusa, Y.Matsuzawa: "Hepatocyte nuclear factor-4alpha gene mutations in Japanese non-insulin dependent diabetes mellitus (NIDDM) patients." Res.Commun.Mol.Pathol.Pharmacol.94 (3). 327-330 (1996)

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

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Published: 1999-03-16  

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