| Project/Area Number |
15H04291
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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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) |
高田 豊行 国立遺伝学研究所, 系統生物研究センター, 助教 (20356257)
宮坂 勇輝 名古屋大学, 医学系研究科, 助教 (30778098)
設楽 浩志 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, 主席基盤技術研究職員 (90321885)
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| Co-Investigator(Renkei-kenkyūsha) |
SEKI Yuta 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, 研究員 (10615636)
YASUDA Shumpei 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, 主任研究員 (50534012)
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| Research Collaborator |
OBARA Yo
SUZUKI Sari
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
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| Keywords | 実験動物学 / 遺伝学 / 難聴 / ゲノム編集 / アレル発現量比較 / コンソミックマウス / カドヘリン23 / 遺伝子発現 / 対立遺伝子発現量 |
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| Outline of Final Research Achievements |
Several inbred strains of mice develop hearing loss (HL) caused by genomic polymorphisms accompanying their genetic backgrounds. To identify the genomic polymorphisms associated with the development of HL, we challenged technological innovations of the forward genetics approach adapted using consomic/congenic mapping, allele-specific gene expression analysis, and genome editing. In particular, this approach was powerful for the identification of genes that are responsible and can rescue HL in C57BL/6J (B6) mice. We discovered that substitutions in a genomic region of chromosome 10 (Chr10) and 12 (Chr12) of MSM/Ms (MSM) mice reduced the symptoms of HL in B6 mice. Moreover, the HL in B6 mice were completely rescued by genome editing of a polymorphism in the gene encoding Cadherin 23 on Chr10 and a genomic substitution of MSM-derived Chr12. In addition, we identified candidate genes on Chr12 associated with HL by congenic mapping and allele-specific gene expression analysis.
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