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Development of murine models of disease using a novel non-obese type 2 diabetes mellitus mouse discovered in Japan and isolation of responsible genes

Research Project

Project/Area Number 21300156
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionResearch Institute for Clinical Oncology, Saitama Cancer Center

Principal Investigator

松島 芳文  埼玉県立がんセンター(臨床腫瘍研究所), 研究員 (10094955)

Project Period (FY) 2009 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2011: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2009: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywords2型糖尿病 / 新生児糖尿病 / 自然発症 / 非肥満 / コンジェニック系 / 糖尿病性腎症 / 疾患モデル / 高脂血症併発モデル / コンジェニック / 自然発症疾患モデル / 高脂血症 / 常染色体性優性遺伝 / ポジショナルクローニング
Research Abstract

The murine models of diabetes reported in the present study are novel models of spontaneous disease. The mice are non-obese and show autosomal dominant inheritance. The type 2 diabetes models are heterozygote strains, whereas the neonatal diabetes mellitus models are homozygote strains that die due to severe hyperglycemia at 4 days after birth. The progenitor mutant mouse was discovered in the F2 population between the two inbred mouse strains NC/Jic and KOR1. Because diabetes is a multifactorial disease and its genetic analysis is difficult, murine models with the same genetic background were developed to isolate modification genes responsible for the onset of diabetes. Hybridization was used to introduce the mutant genes into 10 inbred strains with different genetic backgrounds to create congenic murine models of diabetes and into four apoE-deficient hyperlipidemia mouse (SHL) strains to develop murine models of diabetes with hyperlipidemia. Development of 機関番号:82402 研究種目:基盤研究(B) 研究期 … More 間:2009年度~2012年度 課題番号:21300156 研究課題名(和文) 我国で発見された新規非肥2型糖尿病マウスによる疾患モデル群樹立と原因遺伝子の特定 研究課題名(英文) Development of murine models of disease using a novel non-obese type 2 diabetes mellitus mouse discovered in Japan and isolation of responsible genes 研究代表者 松 島 芳 文 (マツシマ ヨシブミ) 研究者番号:10094955 congenic murine models is completed at the N12 or a later generation. Eight congenic strains for diabetes (AKR, BALB/c, C3H/He, C57BL/6, DBA/2, JF1, NC/Jic, and NC/Nga) and four strains for diabetes with hyperlipidemia (B6.SHL, C.SHL, C3.SHL, and D2.SHL) have been successfully developed in this study. However, A/J and KORI are both at the N6 generation and are being advanced to the later generations to generate congenic strains. These congenic strains showed prominent differences with respect to various phenotypic characteristics, such as age in weeks at urinary sugar manifestation, blood sugar level, and sex difference, at disease onset. Therefore, they also have utility as novel models for personalized medicine. There are, as yet, few reports on the development of diabetic nephropathy models that researchers long for. However, pathological observations of the kidneys of the C57BL/6 congenic strain suggest that it may be a novel model of diabetic nephropathy. Positional cloning of the responsible gene has narrowed down the candidate region to the vicinity of the centromere of the mouse chromosome 8. DNA sequencing is ongoing, and the results there of will be available before manuscript submission. Less

Report

(5 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (15 results)

All 2012 2010 2007 Other

All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (4 results) Remarks (7 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Japanese Wild Mice: A Rich Resource for New Disease Models2012

    • Author(s)
      Yoshibumi MATSUSHIMA
    • Journal Title

      Experimental Animals

      Volume: 61 Issue: 1 Pages: 25-33

    • DOI

      10.1538/expanim.61.25

    • NAID

      10030286627

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 日本産野生マウスからの遺伝子導入と新規疾患モデル2012

    • Author(s)
      松島芳文
    • Journal Title

      アニテックス

      Volume: 24 Pages: 12-19

    • Related Report
      2011 Annual Research Report
  • [Presentation] 新規自然発症新生児糖尿病モデルマウスの発見と原因遺伝子のポジショナルクローニング2012

    • Author(s)
      松島芳文、渡辺潤子、日合弘
    • Organizer
      第26回日本糖尿病・肥満動物学会
    • Place of Presentation
      名古屋市
    • Year and Date
      2012-02-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] 新規自然発症新生児糖尿病モデルマウスの発見と原因遺伝子のポジショナルクローニング2012

    • Author(s)
      松島芳文、日合 弘、渡邊潤子
    • Organizer
      第26回日本糖尿病・肥満動物学会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Final Research Report
  • [Presentation] 新規2型糖尿病マウスDMSのコンジェニック系作出と原因遺伝子のポジショナルクローニングの現状2010

    • Author(s)
      松島芳文、日合弘
    • Organizer
      日本糖尿病肥満モデル学会
    • Place of Presentation
      大阪・ホテルコスモスクエア
    • Year and Date
      2010-01-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] 新規2型糖尿病マウスDMSのコンジェニック系作出と原因遺伝子のポジショナルクローニングの現状2010

    • Author(s)
      松島芳文、日合 弘
    • Organizer
      第24回日本糖尿病・肥満動物学会
    • Place of Presentation
      大阪
    • Related Report
      2012 Final Research Report
  • [Remarks] 埼玉県立がんセンター臨床腫瘍研究所ホームページ

    • URL

      http://www.saitama-cc.jp/rinsyousyuyou_labo/project08.html

    • Related Report
      2012 Final Research Report
  • [Remarks] (動画)新規糖尿病マウス、NC/Nga系コンジェニックマウスへテロ個体

    • URL

      http://www.youtube.com/watch?v=btk_NF7wcnc

    • Related Report
      2012 Final Research Report
  • [Remarks] (動画)新規糖尿病マウス、JF1系コンジェニックマウス新生児糖尿病マウス

    • URL

      http://www.youtube.com/watch?v=tK820-64fIs

    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://www.saitama-cc.jp/rinsyousyuyou_labo/project08.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.saitama-cc.jp/rinsyousyuyou_labo/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.saitama-cc.jp/rinsyousyuyou_labo/index.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.saitama-cc.jp/rinsyousyuyou_labo/index.html

    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] 2型糖尿病モデルマウス2007

    • Inventor(s)
      松島芳文
    • Industrial Property Rights Holder
      埼玉県
    • Acquisition Date
      2007-08-10
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 2型糖尿病モデルマウス2007

    • Inventor(s)
      松島芳文
    • Industrial Property Rights Holder
      埼玉県
    • Acquisition Date
      2007-08-10
    • Related Report
      2012 Final Research Report
    • Overseas

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Published: 2009-04-01   Modified: 2019-07-29  

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