| Project/Area Number |
24650243
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory animal science
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
KIKKAWA Yoshiaki 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, プロジェクトリーダー (20280787)
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| Co-Investigator(Kenkyū-buntansha) |
KURAMOTO Takashi 京都大学, 医学(系)研究科(医学院), 准教授 (20311409)
WADA Kenta 東京農業大学, 生物産業学部, 助教 (20508113)
TAYA Choji 公益財団法人東京都医学総合研究所, 基盤技術研究センター, 動物実験開発室室長 (90175456)
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| Research Collaborator |
WATANABE Kei 筑波大学, 生命環境科学研究科, 博士後期課程
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 育種遺伝 / 遺伝学 / ゲノム / 種差 / 遺伝様式 / Mip / 白内障モデルラット / 白内障モデルマウス / マウス / ラット / 白内障 / CRISPR |
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| Research Abstract |
Although cataract formation caused by major intrinsic protein of lens fiber (Mip) mutations in humans and mice has a dominant mode of inheritance, cataractogenesis in a rat model KFRS4, which has a 5-bp insertion in Mip that truncates the protein, is recessively inherited. To confirm the species-specific differences in the genetic mode of cataractogenesis between humans/mice and rats, we generated new mouse and rat Mip mutants and analyzed their lens phenotypes. First, we created mouse mutants with mutations similar to that in the KFRS4 rat by performing genome editing using CRISPR/Cas9. The heterozygous Mip mutants exhibited severe lens opacity. Next, we screened an ENU mutagenesis library for novel rat Mip mutations and identified two missense mutations located at sites analogous to known mutation sites in human patients. In phenotypic analyses of the lenses, no lens opacity was observed in the rats heterozygous for either Mip mutation.
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