Identification of functional genes in outer hair cells using an inducible depletion mouse model

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06818
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: MATSUOKA Kunie 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, 主席研究員 (40291158)
• Co-Investigator(Renkei-kenkyūsha): 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) ; WADA Kenta 東京農業大学, 生物産業学部, 准教授 (20508113)
• Research Collaborator: MIYASAKA Yuki 名古屋大学, 医学系研究科, 助教 (30778098)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 難聴 / 疾患モデル / 内耳外有毛細胞 / RNA-seq / CRISPR/Cas9システム

Outline of Final Research Achievements

In cochlea, outer hair cells (OHCs) play an essential role in the amplification of sound-induced vibrations. We generated a mouse model that lacks OHCs by administration of diphtheria toxin. We performed differential expression analysis of cochlea-derived mRNAs isolated from the OHC-depleted and control mice using by RNA-seq and microarray methods. We found that the expression of several genes was remarkably decreased in cochlea of OHC-depleted mice. The downregulated genes included causative genes for hearing impairment, such as Myo15, Strc, Pou4f3, Kcnq4, and Slc26a5. Moreover, we identified that the expression of Ocm, Chrna10, Ppp1r17, and Slc6a11, which was also significantly decreased in cochlea of the OHC-depleted mice. Immunohistochemical analysis showed that those genes were exactly expressed in OHCs. Thus, our study provided expression data of several genes that may have potential functional roles in OHCs.

Free Research Field

実験動物学