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Genetic mapping of a susceptibility locus for autoimmune type 1 diabetes in the LETL rat

Research Project

Project/Area Number 05454689
Research Category

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

Allocation TypeSingle-year Grants
Research Field Laboratory animal science
Research InstitutionTokyo Medical University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) SERIKAWA Tadao  Kyoto Uiversity, Medicine, Professor, 医学部, 教授 (30025655)
KANAZAWA Masao  Tokyo Medical College, Medicine, Lecture, 医学部, 講師 (10147184)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1994: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥4,300,000 (Direct Cost: ¥4,300,000)
KeywordsType 1 diabetes mellitus / Susceptibility genes / LETL rat / Insulitis / Non-MHC genes / Linkage analysis / SSLP / microsatellite marker / Autoimmune disease / 遺伝
Research Abstract

The LETL rat, characterizing as rapid onset of insulin-dependent (type 1) diabetes mellitus (IDDM), no sex difference in the incidence of onset, autoimmune destruction of pancreatic B-cells and no significant T-cell lymphopenia, is a desirable animal model for human IDDM (Kawano et al., 1991).
1. We established two substrains, one a diabetes-prone (KDP) and the other a non-diabetic (KND) substrains from the original inbred LETL rats with a low incidence (-20%) of diabetes. The features of KDP rats are highincidence (>70%) of diabetes without lymphopenia and 100% development of mild to severe insulitis at 120-220days of age.
2. We have now demonstrated a first genome-wide scan of non-MHC IDDM susceptibility genes in this animal. By analysis of three crosses, we have mapped a major recessively-acting IDDM susceptibility gene, termed Iddm4, to rat chromosome (Chr) 11. Homozygosity for the KDP allele was strongly associated with development of severe insulitis and onset of IDDM.With comparative mapping study among the rat, mouse and human, the homolog of this gene may be located on human Chr 3 and mouse Chr 16, which suggests that this gene is a novel type of IDDM susceptibility genes.

Report

(3 results)
  • 1995 Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N. Yokoi et al.: "Genetic analysis of autoimmune type 1 diabetes in the LETL rat." (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Komeda, et al.: "Establishment of two substrains, diabetes-prone and non-diabetic, from LETL rats with low incidence of insulin-dependent diabetes mellitus."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N.Yokoi, et al.: "Genetic analysis of autoimmune type 1 diabetes in the LETEL rat."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.KOMEDA 他6名: "Establishment of two substrains,diabetes-prone and non-diabetic,from insulin-dependent diabetic LETL rats with low incidence." (発表予定).

    • Related Report
      1994 Annual Research Report
  • [Publications] N.YOKOI 他8名: "Linkage mapping of insulin-dependent diabetes mellitus(IDDM)susccptibilitygenos to chromosome 11 and 8 in diabetes-prene substrain of LETL rats." (発表予定).

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Komeda 他6名: "Allelic relationships of insulin-dependent diabetes mellitus in BB and LETL rats" Endocrine J.(発表予定).

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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