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Mapping of susceptibility genes to diabetes by high fat diet following QTL analysis of diabetic db mice

Research Project

Project/Area Number 17590936
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionThe University of Tokushima

Principal Investigator

MORITANI Maki  The University of Tokushima, Institute for Genome Research, Research assistant, ゲノム機能研究センター, 学術研究員 (50301312)

Co-Investigator(Kenkyū-buntansha) ITAKURA Mitsuo  The University of Tokushima, Institute for Genome Research, Professor, ゲノム機能研究センター, 教授 (60134227)
INOUE Hiroshi  The University of Tokushima, Institute for Genome Research, Research associate, ゲノム機能研究センター, 助教授 (20294639)
KUNIKA Kiyoshi  The University of Tokushima, Institute for Genome Research, Research assistant, ゲノム機能研究センター, 学術研究員 (30396254)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsQTL / Lepr^<db> mice / fat pad weight / congenic mice / type 2 diabetes / animal model of diabetes / susceptibility gene / feeding volume / 高脂肪食負荷 / 内蔵脂肪量 / 動物モデル
Research Abstract

To identify the susceptibility genes to type 2 diabetes (T2D), we previously identified 2 quantitative trait loci (QTL), which affect body weight, fat pad weight, and fasting blood glucose concentrations in a leptin receptor deficient obese F2 intercross derived from BKS and DBA2 (D2) mice. We also generated congenic mice by repeatingly backcrossing donor (db) mice to recipient D2 mice carrying a given QTL-containing genomic region to test the effect of each QTL on diabetic phenotypes. Introgression of two QTL regions of D2 into BKS background replicated the increase in body weight and fat pad weight. The effect of QTL was dependent on obesity associated with the db/db-induced diabetes. To identify the factors promoting obesity-induced T2D, we conducted genetic studies on two lines of wild type congenic mice (without db loci) with high fat diet. Our findings are as follows ; 1) We found the suitable high fat diet to promote obesity-induced T2D in males and females. 2) We generated congenic mice without db loci by repeatingly backcrossing donor (db) mice to recipient D2 mice. Effects of genomic region were tested by comparing congenic mice having one region from D2 with having BKS alleles. Differences in phenotypes were replicated in body weight and fat pad weight in one line of congenic mice. 3) In another a line, we could not map the locus correlating obesity-induced T2D. 4) In the first line, analyses of six sub-lines identified the target region of eight Mb, which affects body weight induced by high fat diet. Our identification provides insight of obesity-induced type 2 diabetes mellitus.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (18 results)

All 2007 2006 2005

All Journal Article (18 results)

  • [Journal Article] Genetic association of single nucleotide polymorphisms in endonuclease G-like 1 gene with type 2 diabetes in a Japanese population.2007

    • Author(s)
      Maki Moritani
    • Journal Title

      Diabetologia (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Genetic associationof single nucleotide polymorphisms in endonuclease G-like 1 gene with type 2 diabetes in a Japanese population.2007

    • Author(s)
      Maki Moritani
    • Journal Title

      Diabetologia (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification of diabetes susceptibility loci in db mice by combined quantitative trait loci analysis and haplotype mapping.2006

    • Author(s)
      Maki Moritani
    • Journal Title

      Genomics 88

      Pages: 719-730

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Multidimensional genome scans identify the combinations of genetic loci linked to diabetes-related phenotypes in mice.2006

    • Author(s)
      Katsuhiko Togawa
    • Journal Title

      Hum Mol Genet 15

      Pages: 113-128

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Diabetic modifier QTLs identified in F_2 intercrosses between Akita and A/J mice.2006

    • Author(s)
      Shigeru Takeshita
    • Journal Title

      Mamm Genome 17

      Pages: 927-940

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Multidimensional genome scans identify the combinations of genetic loci linked to diabetes-related phenotypes in mice.2006

    • Author(s)
      Katsuhiko Togawa
    • Journal Title

      Hum Mol Gene 15

      Pages: 113-128

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Diabetic modifier QTLs identified in F2 intercrosses between Akita and A/J mice.2006

    • Author(s)
      Shigeru Takeshita
    • Journal Title

      Mamm Genome 17

      Pages: 927-940

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identificationof diabetes susceptibility loci in db mice by combined quantitative trait loci analysis and haplotype mapping.2006

    • Author(s)
      Maki Moritani
    • Journal Title

      Genomics 88

      Pages: 719-730

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effect of +36T>C in intron 1 on the glutamine : fructose-6-phosphate amidotransferase 1 gene and its contribution to type 2 diabetes in different populations.2006

    • Author(s)
      Kiyoshi Kunika
    • Journal Title

      J Hum Genet 51

      Pages: 1100-1109

    • NAID

      10018641703

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genetic association between the PRKCH gene encoding protein kinase Ceta isozyme and rheumatoid arthritis in the Japanese population.2006

    • Author(s)
      Yoichiro Takata
    • Journal Title

      Arthritis & Rheumatism 56

      Pages: 30-42

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Multidimensional genome scans identify the combinations of genetic loci linked to diabetes-related phenotypes in mice.2006

    • Author(s)
      Katsuhiko Togawa
    • Journal Title

      Hum. Mol. Genet. 15

      Pages: 113-128

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Association of single-nucleotide polymorphisms in the suppressor of cytokine signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese.2006

    • Author(s)
      Hitoshi Kato
    • Journal Title

      Genomics 87

      Pages: 446-458

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hypoplasia of endocrine and exocrine pancreas in homozygous transgenic TGF-β1.2005

    • Author(s)
      Maki Moritani
    • Journal Title

      Mol Cell Endocrinol 229

      Pages: 175-184

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of candidate genes in type 2 diabetes modifier locus using expression QTL.2005

    • Author(s)
      Hiroshi Yaguchi
    • Journal Title

      Genomics 85

      Pages: 591-599

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of candidate genes in type 2 (T2D) diabetes modifier locus using expression QTL.2005

    • Author(s)
      Hiroshi Yaguchi
    • Journal Title

      Genomics 85

      Pages: 591-599

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hypoplasia of endocrine and exocrine pancreas in homozygous transgenic TGF-betal.2005

    • Author(s)
      Maki Moritani
    • Journal Title

      Mol. Cell Endocrinol. 229

      Pages: 175-184

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Association between single-nucleotide polymorphisms in the SEC8L1 gene, which encodes a subunit of the exocyst complex, and rheumatoid arthritis in a Japanese population.2005

    • Author(s)
      Daisuke Hamada
    • Journal Title

      Arthrtis Rheum. 52

      Pages: 1371-1380

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Molecular cloning and characterization of the murine gnathodiaphyseal dysplasia gene GDD1.2005

    • Author(s)
      Satoshi Tsutsumi
    • Journal Title

      Biochem. Biophys. Res. Commun. 331

      Pages: 1099-1106

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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