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Identification of susceptibility gene of diabetes mellitus by QTL analysis in the genetic modified mice

Research Project

Project/Area Number 13470227
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

ITAKURA Mitsuo  The University of Tokushima, Institute for Genome Research, Division of Genetic Information, professor, ゲノム機能研究センター, 教授 (60134227)

Co-Investigator(Kenkyū-buntansha) YAMAOKA Takashi  The University of Tokushima, Institute for Genome Research, Division of Genetic Information, research associate, ゲノム機能研究センター, 助教授 (40263826)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2001: ¥6,400,000 (Direct Cost: ¥6,400,000)
Keywordsmultifactorial disease / modifier gene for diabetes / type II diabetes / QTL analysis / db mice / susceptibility gene / animal model for diabetes / F2 intercross mice / コンジェニックマウス / スピードコンジェニック / サブ-コンジェニックマウス / 修飾遺伝子 / ロッドスコア / 疾患病モデル動物
Research Abstract

Diabetes is one of the typical "common diseases" and a major public health problem in Japan. Type 2 diabetes mellitus (T2D) results from the interaction between "genetic" and "environmental" factors. It is very important to identify the disease-susceptibility genes of diabetes. Mouse models of human diseases offer a powerful method to analyze human diseases. To identify the susceptibility genes of T2D, we performed genome-wide quantitative trait loci (QTL) analysis in 788 F_2 intercross generation between db mice carrying a mutation of leptin receptor (BKS-db/+m) with C3H/HeJ (C3H) mice. db mouse (BKS-db/db) having a mutation in the leptin receptor gene, is an animal model for T2D in humans
The phenotypes, including body weight, fasting blood glucose (BG) concentrations, fat weight, and intraperitoneal glucose tolerance test were determined. Correlation between genotypes with the whole genome 203 microsatellite markers and these quantitative phenotypes, were examined in a diabetic group including those homozygous for db (F_2-db/db) and a non-diabetic group including those heterozygous (F2 db/+m} and wild type (F_2-wild) for db. Vie found 18 QTLs (Lod Score >2.8 of suggestive value} for diabetes-related phenotypes including body weight, fat weight, and glucose tolerance. These loci also provide the susceptibility candidate regions to diabetes in humans. Production of the congenic mice is under way in our laboratory

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (47 results)

All Other

All Publications (47 results)

  • [Publications] Masao Kitabayashi, et al.: "Gene Clonig and polymerase Chain Reaction with Proliferating Cell Nuclear Antigen from Thermococcus Kodakaraensis KOD1."Biosci, Biotechnol.Biochem.. 66(10). 2194-2200 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoshi Tsutsumi, et al.: "Autosomal Dominant Gnathodiaphyseal Dysplasia Maps to Chromosome 11p14.3-15.1."J.Bone Miner.Res.. 18. 413-418 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Soichi Honda, et al.: "Human Pituitary Adenomas Infrequency Contain Inactivation of Retinoblastoma 1 Gene and Activation of Cyclin Dependent Kinase 4 Gene."Endocr.J.. 50(3). 309-318 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Eiji Kudo, et al.: "Familial Juvenile Hyperuricemic Nephropathy : Detection of Mutation in the Uromodulin Gene in 5 Japanese Families."Kidney.Int.. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Setsuo Ii, et al.: "Redox State-Dependent and Sorbitorl Accumulation-Independent Diabetic Albuminuria Study on Human Aldose Reductase-Transgenic and Sorbitol Dehydrogenase-Deficient Mice"Diabetologia. 47. 541-548 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoshi Tsutsumi, et al.: "The Novel Gene Encoding an Eight Transmenbrane Spanning Domein Protein is Mutated in Gnthodiaphyseal Dysplasia."Am.J.Hum.Genet.. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takashi Yamaoka, et al.: "Feedback Inhibition of Amidophosphoribosyltransferase Regulates the Rate of Cell Growth via Purine Nucleotide, DNA, and Protein Syntheses."J.Biol.Chem.. 276(24). 21285-21291 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takashi Yamaoka: "Gene Therapy for Diabetes Mellitus."Curr.Mol.Med.. 1. 325-337 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takashi Yamaoka, et al.: "Regenerative Therapy of Pancreatic β Cells toward a Cure for Diabetes?"Biochem.Biophys.Res.Commun. 296(5). 1039-1043 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwano Ohno, et al.: "Familial Juvenile Gouly Nephropathy : Exclusion of 16p12 from the Candidate locus."Nephron. 92. 573-575 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takashi Yamaoka, et al.: "Transgenic Expression of FGF8 and FGF10 Induces Transdifferentiation of Islet Cells into Hepatocytes and Exocrine Cells."Biochem.Biophys.Res.Commun.. 292. 138-143 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masumi Nichi, et al.: "A Missense Mutation Myostatin Causes Hyperplasia without Hypertrophy in the Mouse Muscle."Biochem.Biophys.Res.Commun.. 293(1). 247-251 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 山岡 孝: "糖尿病の遺伝子治療は可能か?"分光堂. 9 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 森谷 眞紀: "ポストゲノム時代の遺伝統計学"株式会社 羊土社. 11 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takashi Yamaoka, et al.: "Feedback Inhibition of Amidophosphoribosyltransferase Regulates the Rate of Cell Growth via Purine Nucleotide, DNA, and Protein Syntheses"J.Biol.Chem.. 276(24). 21285-21291 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takashi Yamaoka: "Gene Therapy for Diabetes Mellitus"Curr.Mol.Med. 1. 325-337 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takashi Yamaoka et al.: "Regenerative Therapy of Pancreatic β Cells toward a Cure for Diabetes ?"Biochem.Biophys.Res.Commun.. 296(5). 1039-1043 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwano Ohno, et al.: "Familial Juvenil Gouty Nephropathy : Exclusion of 16p12 from the Candidate Locus"Nephron. 92. 573-575 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takashi Yamaoka, et al.: "Transgenic Expression of FGF8 and FGF10 Induces Transdifferentiation of Islet Cells into Hepatocytes and Exocrine Cells"Biochem.Biophys.Res Commun. 292. 138-143 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masumi Nichi, et al.: "A Missense Mutation Myostatin Causes Hyperplasia without Hypertrophy in the Mouse Muscle"Biochem.Biophys.Res Commun.. 293(1). 247-251 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masao Kitabayashi et al.: "Gene Cloning and Polymerase Chain Reaction with Proliferating Cell Nuclear Anti en from Thermococcus Kodakaraensis KOD1"Biosci.Biotechnol.Biochem.. 66(10). 2194-2200 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoshi Tsutsumi, et al.: "Autosomal Dominant Gnathodiaphyseal Dysplasia Maps to Chromosome 11p14.3-15.1"J.Bone Miner.Res. 18. 413-418 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Soichi Honda, et al.: "Human Pituitary Adenomas Infrequency Contain Inactivation of Retioblastoma 1 Gene and Activation of Cyclin Dependent Kinase 4 Gene"Endorc.J.. 50(3). 309-318 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Eiji Kudo, et al.: "Familial Juvenile Hyperuricemic Nephropathy : Detection of Mutation in the Uromodulin Gene in 5 Japanese Families"Kidney Int.. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Setsuo Ii, et al.: "Redox State-Dependent and Sorbitorl Accumulation-Independent Diabetic Albuminuria Study on Human Aldose Reductase-Transgenic and Sorbitol Dehydrogenase-Deficient Mice"Diabetologia. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoshi Tsutsumi, et al.: "The Novel Gene Encoding an Eight Transmembrane Spanning Domein Protein Is Mutated in Gnthodiaphyseal Dysplasia"Am.J.Hum.Genet.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maki Moritani: "Genetic Statistics in Post Genome"Youdo Inc.. 11 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takashi Yamaoka: "Gene Therapy for Diabetes Mellitus"Bunkoudo Inc.. 9 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoshi Tsutsumi, et al.: "Autosomal Dominant Gnathodiaphyseal Dysplasia Maps to Chromosome 11p14.3-15.1"J.Bone Miner.Res. 18. 413-418 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takashi Yamaoka, et al.: "Regeneration Therapy for Diabetes Mellitus"Expert.Opin.Biol.Ther.. 3(3). 425-433 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Soichi Honda, et al.: "Human Pituitary Adenomas Infrequency Contain Inactivation of Retinoblastoma 1 gene and Activation of Cyclin Dependent Kinase 4 Gene"Endocr.J.. 50(3). 309-318 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Eiji Kudo et al.: "Familial Juvenile Hyperuricemic Nephropathy : Detection of Mutation in the Uromodulin Gene 5 Japanese Families"Kidney Int.. (in press). (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Setsuo Ii, et al.: "Redox State-Dependent and Sorbitorl Accumulation-Independent Diabetic Albuminuria Study on Human Aldose Reductase-Transgenic and Sorbitol Dehydrogenase Deficient Mice"Diabetologia. 47. 541-548 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Satoshi Tsutsumi, et al.: "The Novel Gene Encording an Eight Transmembrane Spanning Domein Protein is Mutated in Gnthodiaphyseal Dysplasia"Am.J.Hum.Genet.. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takashi Yamaoka: "Regenerative Therapy of Pancreatic β Cells toward a Cure for Diabetes"Biochem. Biophys. Res. Commun.. 296(5). 1039-1043 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takashi Yamaoka: "Transgenic Expression of FGF8 and FGF10 Induces Transdifferentiation of Islet Cells into Hepatocytes and Exocrine Cells"Biochem. Biophys. Res. Commun.. 292(1). 138-143 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masumi Nichi: "A Missense Mutant Myostatin Causes Hyperplasia without Hypertrophy in the Mouse Muscle"Biochem. Biophys. Res. Commun.. 293(1). 247-251 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwao Ohno: "Familial Juvenile Gouty Nephrophathy Exclusion of 16p12 from the Candidate Locus"Nephron. 92. 573-575 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takashi Yamaoka: "Regeneration Therapy of Pancreatic β Cells"Expert Opin. Biol. Ther.. (in press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Satoshi Tsutsumi: "Autosomal Dominant Gnathodiaphyseal Dysplasia Maps to Chromosome 11p14.3-15.1"J. Bone Miner. Res.. 18(3). 413-418 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山岡 孝: "遺伝子導入マウスによる糖尿病モデルと膵島再生ヒト疾患モデル"文光堂(in press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takashi Yamaoka: "Feedback Inhibition of Amidophosphoribosyltransferase Regulates the Rate of Cell Growth via Purine Nucleotide, DNA, and Protein Syntheses"J. Biol. Chem.. 276(24). 21285-21291 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takashi Yamaoka: "Gene Therapy for Diabetes Mellitus"Curr. Mol. Med.. 1. 325-337 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujio Takeuchi: "HLA-DR Shared Epitope in Familial Cases of Japanese Rheumatiod Arthritis"Clin. Exp. Rheumatol.. 18. 424-426 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takashi Yamaoka: "Regenerative Therapy of Pancreatic β Cells toward a Cure for Diabetes"Biochem. Biophys. Res. Commun. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takashi Yamaoka: "Transgenic Expression of FGF8 and FGF10 Induces Transdifferentiation of Islet Cells into Hepatocytes and Exocrine Cells"Biochem. Biophys. Res. Commun.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] "ポストゲノム時代の遺伝統計学"315 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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