| Project/Area Number |
15K18393
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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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 |
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)
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| Research Collaborator |
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)
SHITARA Hiroshi 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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| 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 |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 遺伝学 / 実験動物学 / ミオシンVI / ゲノム多型 / 有毛細胞 / 難聴 / ゲノム編集 / モデルマウス / 機能ゲノム多型 / ヒト変異模倣マウス / 進行性難聴 |
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| Outline of Final Research Achievements |
The early-onset progressive hearing loss (ePHL) in heterozygotes of the wild-type and ksv allele of Myosin VI gene (Myo6) was accelerated by genetic background effect of C57BL/6J (B6) mice. To identify a polymorphism(s) associated with the ePHL, we performed a genetic mapping approach using a backcross progeny with MSM/Ms mice. This approach discovered that ePHL strongly associates with cadherin 23 gene (Cdh23), which is associated with the onset of hearing loss, on chromosome 10. We confirmed that c.753G>A genome editing of Cdh23 reduce the symptoms of ePHL in ksv/+ mice. However, the ePHL were not completely rescued by the genome editing; therefore, this result suggests that the other polymorphisms accompanying the genetic background of B6 mice contribute the severity and acceleration of ePHL in ksv/+ heterozygous mice.
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