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Construction of a fine genetic map in the rat model of type 1 diabetes for positional cloning

Research Project

Project/Area Number 07458229
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionTokyo Medical College

Principal Investigator

KOMEDA Kajuro  Tokyo Medical College, Medicine, Assistant Professor, 医学部, 助教授 (90074533)

Co-Investigator(Kenkyū-buntansha) SERIKAWA Tadao  Kyoto University, Medicine, Professor, 医学研究科, 教授 (30025655)
KANAZAWA Masao  Tokyo Medical College, Medicine, Lecture, 医学部, 講師 (10147184)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥3,900,000 (Direct Cost: ¥3,900,000)
KeywordsType 1 diabetes / Susceptibility gene / Non-MHC gene / KDP rat / Linkage analysis / Comparative mapping / Microsatellite maker / Insulitis
Research Abstract

The Long-Evans Tokushima Lean (LETL) rat, characterized by rapid onset of insulin-dependent (type 1) diabetes mellitus (IDDM), no sex difference in the incidence of IDDM,autoimmune destruction of pancreatic beta-cells, and no significant T-cell lymphopenia, is a desirable animal model for human IDDM.The first genetic analysis showed that an MHC-linked gene is involved in the pathogenesis of insulitis. So far, other genetic factors have not been revealed due to a low incidence (about 20%) of IDDM in this strain. We have established a diabetes-prone substrain of the LETL rat, named Komeda Diabetes-Prone (KDP) rat, showing a 100% development of insulitis and over 70% incidence of IDDM within 220 days. In this study, we performed the first genom-wide scan for non-MHC IDDM susceptibility genes in the KDP rat and identified a major IDDM susceptibility gene, termed Iddm/kdp1, in the region between Mox2 and D11M16Mit46 on rat chromosome (Chr) 11. Homozygosity for the KDP allele at this locus is shown to be essential for the development of moderate to severe insulitis and the onset of IDDM.Comparative mapping suggests that homologues of Iddm/kdp1 are located on human Chr 3 and mouse Chr 16 and would therefore be different from previous reported IDDM susceptibility genes. (J.Clin.Invest.1997.100 : 2015-2021.)

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] T. Maihara et al.: "Fifty-six new microsatellite markers in the rat genetic linkage map" Transpl. Proc.27. 1502-1504 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.yokoi et al.: "Mopping of 20 polymorphic DNA markers in the rat by somatic hybrid and linkage analysis." Mamm. Genome. 7. 71-73 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 横井 伯英 ら: "新しく開発されたI型糖尿病モデルラット(KDP)における病因遺伝子の遺伝学的解析" 日本疾患モデル学会記録. 13. 61-70 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N. Yokoi et al.: "A Non-MHC Locus Essential for Autoimmune Type I Diabetes in the Komeda Drabetes-Prone Rat" J. Clin Invest.100. 2015-2021 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K. Komeda st al.: "Establishment of two substrains, diabetes-prone and non-diabetic, from LETL rats." (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Maihara, Y.ando, N.Yokoi, T.Kuramoto, and T.Serikawa: "Fifty-six new microsatellite markers in the rat genetic linkage map" Transpl.Proc.27. 1502-1504 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Yokoi, K.Kitada, T.Kuramoto, T.Maihara, J.Higaki, T.Miki, T.Ogihara, and T.Serikawa: "Mapping of 20 polymorphic DNA markers in the rat by somatic hybrid and linkage analysis." Mamm.Genome. 7. 71-73 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Yokoi, M.Kanazawa, K.Kitada, A.Tanaka, Y.Kanazawa, S.Suda, H.Ito, T.Serikawa, and K.Komeda: "A no-MHC locus essential for autoimmune Type 1 diabetes in the Komeda Diabetes-Prone (KDP) rat." J.Clin.Invest.100. 2015-2021 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Komeda, M.Noda, K.Terao, H.Iwama, Y.Yamada, N.Kuzuya, M.Kanazawa, and Y.Kanazawa: "Establishment of two substrains, diabetes-prone and non-diabetic, from LETL rats."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Maihara et al.: "Fifty-six new microsatellite markers in the rat genetic linkage map." Transpl.Proc.27. 1502-1504 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Yokoi et al.: "Mapping of 20 polymorphic DNA markers in the rat by somatic hybrid and likage analysis." Mamm.Genome. 7. 71-73 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 横井伯英ら: "新しく開発されたI型糖尿病モデルラット(KDP)における病因遺伝子の遺伝学的解析" 日本疾患モデル学会記録. 12(印刷中).

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Komeda et al.: "Establishment of two substrains,diabetes-prone and non-diabetic,from LETL ratswith low incidence of insulin-dependent diabetes mellitus." 発表予定.

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Yokoi et al.: "Demonstration of a non-MHC gene as an essential component for autoimmune Type 1 diabetes in the Komeda Diabetes-Prone(KDD) rat." 発表予定.

    • Related Report
      1996 Annual Research Report
  • [Publications] Yokoi, N.: "Mapping of 20 polymorphic DNA markers in the rat by somatic hybrid and linkage analysis." Mamm. Genome. 7. 71-73 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Komeda, K.: "Establishment of two substrains, deabetes-prone and non-diabetic, from LETL rats with low incidence of insulin-dependent diabetes mellitus." (発表予定).

    • Related Report
      1995 Annual Research Report
  • [Publications] Yokoi, N.: "Genetic analysis of autoimmune type 1 diabetes in the LETL rat" (発表予定).

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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