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

Research Project

Project/Area Number 09470224
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 InstitutionThe University of Tokushima

Principal Investigator

ITAKURA Mitsuo  Inst. For Genome Research, Univ. Tokushima professor, ゲノム機能研究センター, 教授 (60134227)

Co-Investigator(Kenkyū-buntansha) IKEGAMI Hiroshi  Sch. Med., Univ. Osaka research associate, 医学部, 助手 (20221062)
MORITANI Maki  Sch. Med., Univ. Tokushima research associate, 医学部, 助手 (50301312)
YAMAOKA Takeshi  Sch. Med., Univ. Tokushima research associate, 医学部, 助手 (40263826)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1999: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1997: ¥6,000,000 (Direct Cost: ¥6,000,000)
Keywordsdb mice / NOD-RGP-IL-10 Tg / type I diabetes / QTL analysis / type II diabetes / animal model for diabetes / common disease / susceptibility gene / 糖尿病の修飾遺伝子 / I型糖尿病 / II型糖尿病 / 連鎖解析 / 糖尿病修飾遺伝子 / QTL / 分子生物学
Research Abstract

Type I and II diabetes is a common disease and a major public health problem. To identify the susceptibility gene to diabetes we performed genome-wide quantitative trait loci (QTL) analysis, using db mice in C57BL6/ksj background or NOD-RGP-IL-10 Tg in NOD background. db mouse is an animal model of type II diabetes in human exhibiting hyperglycemia, hyperinsulinemia, insulin resistance, and obesity. F2 intercross between db mice and non-diabetic C3H strain demonstrated a wide variety of diabetes related, including body weight, plasma glucose concentration, plasma insulin concentration, and glucose tolerance. We have identified several QTLs associated with body weight and glucose tolerance. NOD-RGP-IL-10 Tg enhance autoimmune diabetes, but none of the resulting F1 mice outbred to C57BL/6 mice show diabetes. N2 backcross between NOD-RGP-IL-10 Tg and C57BL/6 mice demonstrated 15% incidence of diabetes. Similar to db mice, we are performing genome-wide quantitative trait loci (QTL) analysis for N2 generation.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Yamaoka T: "Diabetes and pancreatic tumors in transgenic mice expression pax 6"Diabetologia. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sasahara K: "Molecular cloning and expression analysis of a putative nuclear protein,SR-25"Biochem.Biophys.Res.Commun.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kamatani N: "Localization of a gene for familial juvenile Hyperuricemic nephropathy causing undcrecerection-type gout to I6p12 by genome-wide linkage analysis of a large family"Arthritis & Rheumatism. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamaoka T: "Apoptosis and remodelling of beta cell by paracrine interferon-γ without insulitis in transgenic mice"Diabetologia. 42. 566-573 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Moritai M: "Abrogation of autoimmune diabetes in non-obese deabetic mice and protection against effector lymphocytes by transgenic paracrine TGF-β1"J.Clin.Invest.. 102(3). 499-506 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamaoka T: "Hypoplasia of pancreatic islets in transgenic mice expressing activin receptor mutants"J.Clin.Invest.. 102(2). 294-301 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 森谷眞紀、板倉光夫: "遺伝子治療・開発研究ハンドブック、遺伝病、多遺伝子性疾患"株式会社エス・エヌ・ティ. 1061 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 森谷眞紀、板倉光夫: "糖尿病の遺伝子診断、遺伝子治療入門"名古屋大出版(in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamaoka T.: "Diabetes and pancreatic tumors in transgenic mice expression pax 6."Diabetologia. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sasahara K.: "Molecular cloning and expression analysis of a putative nuclear protein, SR-25"Biochem. Biophys. Res. Commun.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kamatani N.: "Localization of a gene for familial juvenile hyperuricemic nephoropathy causing underexcretion-type gout to 16p12 by genome-wide linkage analysis of a"Arthritis & Rheumatism. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamaoka T.: "Apoptosis and remodelling of beta cells by paracrine interferon-γ without insulitis in transgenic mice."Diabetologia. 42. 566-573 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Moritai M.: "Abrogation of autoimmune diabetes in non-obese diabetic mice and protection against effector lymphocytes by transgenic paracrine TGF-β1."J. Clin. Invest. 102(3). 499-506 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamaoka T.: "Hypoplasia of pancreatic islets in transgenic mice expressing activinre ceptor mutants."J. Clin. Invest.. 102(2). 294-301 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Moritai M., Itakura M.: "Handbook of gene therapy : Genetic disease, Polygenic disease"S.N.T. Inc.. 1061 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Moritai M., Itakura M.: "Genetic testing for Diabetes"Nagoya University Press (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamaoka T: "Diabetes and pancreatic tumors in transgenic mice expression pax 6."Diabetologia. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sasahara K: "Molecular cloning and expression analysis of a putative nuclear protein,SR-25."Biochem.Biophys.Res.Commun.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kamatani N: "Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p 12 by genome-wide linkage analysis of a large family."Arthritis & Rheumatism. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamaoka T: "Apoptosis and remodelling of beta cells by paracrine interferon-γ without insulitis in transgenic mice."Diabetologia. 42. 566-573 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Moritai M: "Abrogation of autoimmune diabetes in non-obese diabetic mice and protection against effector lymphocytes by transgenic paracrine TGF-β1."J.Clin.Invest.. 102(3). 499-506 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamaoka T: "Hypoplasia of pancreatic islets in transgenic mice expressing activin receptor mutants."J.Clin.Invest.. 102(2). 294-301 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 森谷眞紀、板倉光夫: "遺伝子治療・開発研究ハンドブック、遺伝病、多遺伝子性疾患"株式会社エス・エヌ・ティ. 1061 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 森谷眞紀、板倉光夫: "糖尿病の遺伝子診断、遺伝子治療入門"名古屋大出版(in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamaoka T: "Amidophosphoribosyltransferase limits the rate of cell growth-liked de novo purine biosynthesis in the presence of constant capacity of salvage purine biosynthesis." J.Biol.Chem.272. 17719-17725 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tomonari A: "Identification of cis-Acting DNA elements of the human γ-glutamylcysteine synthetase heavy subunit gene." Biochem.Biophys.Res.Commun.232. 522-527 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka C: "Infrequent mutations of p27Kip1 gene and trisomy 12 in a subset of human pituitary adenomas." J.Clin.Endocrinol.Metab.82(9). 3141-3147 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsushita T: "Molecular cloning of mouse paired-box-containing gene(pax)-4 from an islet β cell line and deduced sequence of human pax-4." Biochem.Biophys.Res.Commun.242. 176-180 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Moritani M: "Abrogation of autoimmune diabetes in non-obese diabetic mice and protection against effector by transgenic paracrine TGF-β1." J.Chin.Invest.102(3). 499-506 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamaoka T: "Hypoplasia of pancreatic islets in transgenic mice expressing activen receptor mutants." J.Clin.Invest.102(2). 294-301 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamaoka T: "Amidophosphoribosyl transferase limits the rate of cell growth-liked de novo purine biosynthesis in the presence of constant capacity of salyage purine biosynthesis." J.Biol.Chem.272. 17719-17725 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tomonari A: "Identification of cis-Acting DNA elements of the human γ-glutamylcysteine synthetase heavy subunit gene." Biochem.Biophys.Res.Commun.232. 522-527 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka C: "Infrequent mutations of p27Kip1 gene and trisomy 12 in a subset of human pituitary adenomas." J.Clin.Endocrinol.Metab.82(9). 3141-3147 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kunika K: "Damage of charge-dependent renal tubular reabsorption causes diabetic microproteinuria." Diabet.Res.Clin.Pract.36. 1-9 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tomonari A: "Proximal nucleotide sequence of the human γ-glutamylcysteine synthetase heavy subunit gene is involved in cisplatin-induced transcriptional up regulation in a lung-cancer cell line SBC3." Biochem.Biophys.Res.Commun.246. 616-620 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsushita T: "Molecular cloning of mouse paired-box-containing gene(pax)-4 from an islet β cell line and deduced sequence of human pax-4." Biochem.Biophys.Res.Commun.242. 176-180 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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