Function of scaffold proteins in the polarization of stereocilia on inner ear hair cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K20239
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: 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)
• 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: Usher症候群 / 平面内細胞極性 / 不動毛

Outline of Final Research Achievements

Sans and Whirlin genes encode scaffold proteins that are known to play a key role in the development of stereocilia in inner ear hair cells. We have found that Sans and Whirlin double-mutant mice showed abnormal polarization of stereocilia. To investigate the mechanisms of the abnormal polarization of stereocilia, we performed comparative phenotypic and gene expression analyses among wild-type mice as well as single- and double-mutant mice carrying mutations in Sans and Whirlin. In the phenotypic analysis, we found that Sans and Whirlin double-mutant mice developed significant mislocalization of kinocilia, although single mutants of either genes showed normal localization of the kinocilia. RNA-seq was also used to also detect specific gene expression changes in the double-mutant mice. Thirty-nine genes were significantly changed in the cochlea of the double-mutant mice. Moreover, we identified a gene associated with the Wnt/PCP signaling pathway in the protein-coding genes.

Free Research Field

マウス遺伝学