Hu Qun, Guo Li, Li Jie, Song Chenmeng, Yu Lisheng, He David Z Z, Xiong Wei
Tsinghua-IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing, China.
Department of Otolaryngology, Peking University People's Hospital, Beijing, China.
Front Mol Neurosci. 2018 Sep 11;11:326. doi: 10.3389/fnmol.2018.00326. eCollection 2018.
Auditory hair cells possess stunning cilia structure that composes of a bundle of stereocilia for mechano-electrical transduction and a single kinocilium for guiding the polarity of hair bundle towards maturation. However, the molecules underlying kinocilium function have not yet been fully understood. Hence, the proteins involved in hair bundle development and function are of a large interest. From a fine microarray analysis, we found that () was enriched in hair cell specific expression profile. Consistently, it has been reported that KNCN was a protein mainly located in the kinocilium of hair cells in the inner ear. However, the hypothesis that KNCN is a kinocilium protein has not been validated in mice with gene perturbed. In this study, we generated knockout mouse lines by CRISPR/Cas9 technique and further examined the morphology and function of cochlear hair cells. Our results showed that there was no obvious hearing loss in the knockout mice, determined by audiometry. Histological study demonstrated that the inner ear and hair cell structure were intact. Especially, there was no deficit of mechanotransduction (MET) in cochlear outer hair cells (OHCs). In summary, our work suggests that KNCN is not essential for kinocilium-oriented hair bundle function in cochlear hair cells.
听觉毛细胞具有令人惊叹的纤毛结构,它由一束用于机械 - 电转导的静纤毛和一根用于引导毛束极性走向成熟的动纤毛组成。然而,动纤毛功能背后的分子机制尚未完全被理解。因此,参与毛束发育和功能的蛋白质备受关注。通过精细的微阵列分析,我们发现( )在毛细胞特异性表达谱中富集。一致的是,据报道KNCN是一种主要位于内耳毛细胞动纤毛中的蛋白质。然而,KNCN是动纤毛蛋白这一假设在基因被干扰的小鼠中尚未得到验证。在本研究中,我们通过CRISPR/Cas9技术构建了KNCN基因敲除小鼠品系,并进一步检测了耳蜗毛细胞的形态和功能。我们的结果表明,通过听力测定,基因敲除小鼠没有明显的听力损失。组织学研究表明内耳和毛细胞结构完整。特别是,耳蜗外毛细胞(OHCs)的机械转导(MET)没有缺陷。总之,我们的工作表明KNCN对于耳蜗毛细胞中动纤毛导向的毛束功能并非必不可少。