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論文
- タイトル
- タイトル（英）
- Dominant effect of a single amino acid mutation in the motor domain of myosin VI on hearing in mice.
- 参照URL
- https://researchmap.jp/glirulus/published_papers/48808653
- 著者
- 著者（英）
- Yuta Seki,Shumpei P Yasuda,Xuehan Hou,Kayoko Tahara,Ornjira Prakhongcheep,Ai Takahashi,Yuki Miyasaka,Hirohide Takebayashi,Yoshiaki Kikkawa
- 担当区分
- 概要
- 概要（英）
- An unconventional myosin, myosin VI gene (MYO6), contributes to recessive and dominant hearing loss in humans and mice. The Kumamoto shaker/waltzer (ksv) mouse is a model of deafness resulting from a splice-site mutation in Myo6. While ksv/ksv homozygous mice are deaf due to cochlear hair cell stereocilia fusion at the neonatal stage, the hearing phenotypes of ksv/+ heterozygous mice have been less clear. Due to this splicing error, most MYO6 protein expression is lost in ksv mice; however, MYO6 with a single amino acid mutation (p.E461K) remains expressed. In this study, we investigated the hearing phenotypes and effect of a p.E461K mutation in ksv/+ heterozygous mice. Hearing tests indicated that hearing loss in ksv/+ mice arises concurrently at both low and high frequencies. In the low-frequency region, stereocilia fusions were detected in the inner hair cells of ksv/+ mice. Expression analysis revealed abnormal MYO6 expression and localization, along with atypical expression of proteins in the basal region of the stereocilia, suggesting that these abnormalities may contribute to stereocilia fusion in ksv/+ mice. Conversely, although the expression patterns of MYO6 and stereociliary basal-region proteins appeared normal in the cochlear area corresponding to high-frequency sounds, stereocilia loss in the outer hair cells was observed in ksv/+ mice. These findings suggest that the ksv/+ mice exhibit distinct mechanisms underlying hearing loss across areas responsible for low- and high-frequency hearing, differing from those previously reported in heterozygous Myo6 mice with loss-of-function and missense mutant alleles.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Experimental animals
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2024年12月17日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1538/expanim.24-0141
- 共同研究・競争的資金等の研究課題