Identification of the functional genomic polymorphisms affecting mouse progressive hearing loss

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K18393
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• 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)
• 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)
• Project Period (FY): 2015-04-01 – 2018-03-31
• 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

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.

Free Research Field

哺乳類遺伝学