Article record

CASZ1调控外毛细胞成熟并且是小鼠听力所必需的

CASZ1 regulates the maturation of outer hair cells and is required for hearing in mice.

基础研究耳科IF 5Q1

文献信息

PMID	42707066
原文	在 PubMed 查看原文 ↗
发表日期	2026
作者	Yoko Nakano 查看其他 12 位作者 Elizabeth C Driver；Ning Hu；Braulio Peguero；Susan C Wiechert；Erich T Boger；Chantal Allamargot；Rebecca Hipp；Angelika Doetzlhofer；Steven H Green；Robert J Morell；Matthew W Kelley；Botond Bánfi
作者单位	Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. 查看其他 8 条单位信息 Inflammation Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.；Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.；Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242, USA.；Genomics and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.；Central Microscopy Research Facility, University of Iowa, Iowa City, IA 52242, USA.；The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.；Department of Otolaryngology-Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.；Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
期刊	iScience
SCI 分区	Q1
IF	5
研究类型	基础研究 · 基础／转化
所属专科	耳科

中文摘要

转录因子ATOH1是耳内机械感觉毛细胞（HC）发育的主要调控因子。在此，我们报道其靶基因Casz1调控外毛细胞（OHC）的成熟。在小鼠耳蜗发育期间（而非发育后）遗传性敲除Casz1导致：听力损失；OHC中机械感觉静纤毛束排列紊乱；OHC表皮板中F-肌动蛋白密度降低；进行性OHC丢失；以及内毛细胞（IHC）的轻度形态学改变。该敲除还改变了基因表达，延迟了未成熟OHC中表达基因的下调，包括编码肌动蛋白调节因子的基因Coro2a，并加速了成熟OHC中表达基因的上调。在Casz1突变小鼠中敲除Coro2a恢复了表皮板中的F-肌动蛋白密度，但增加了静纤毛束排列紊乱和听力阈值，揭示CORO2A提供总体有益效应。我们的数据表明，CASZ1调控OHC的转录和形态学成熟，并且成熟中HC中的CASZ1是听力所必需的。

英文摘要

The transcription factor ATOH1 is a master regulator of mechanosensory hair-cell (HC) development in the ear. Here, we report that its target gene Casz1 regulates the maturation of outer HCs (OHCs). Genetic deletion of Casz1 during (but not after) cochlear development in the mouse caused: hearing loss; disorganization of mechanosensory stereocilia bundles in OHCs; reduced F-actin density in OHC cuticular plates; progressive OHC loss; and mild morphological alterations in inner HCs. This deletion also altered gene expression, delaying downregulation of genes expressed in immature OHCs, including the actin regulator-encoding gene Coro2a, and accelerating upregulation of genes expressed in mature OHCs. Deleting Coro2a in Casz1 mutant mice restored F-actin density in cuticular plates but increased stereocilia bundle disorganization and hearing thresholds, revealing that CORO2A provides an overall beneficial effect. Our data indicate that CASZ1 regulates transcriptional and morphological maturation of OHCs, and that CASZ1 in maturing HCs is necessary for hearing.