上海交通大学医学院杨涛团队研究出ATP6V1C1缺乏会损害听觉和前庭毛细胞功能，导致人和小鼠的感觉神经性听力损失。相关论文发表在2026年1月13日出版的《遗传学报》杂志上。

编码v-ATP酶亚基的多个基因与各种形式的综合征性听力损失有关。它们在毛细胞中的功能尚不清楚，毛细胞是听力和平衡所需的关键感觉细胞。在本研究中，对一个非综合征性耳聋的常染色体显性大家族进行连锁分析和外显子组测序，鉴定出ATP6V1C1中编码v-ATPase C1亚基的致病性p.R281P变异。无主题毛细胞Atp6v1c1的条件敲除（CKO）可导致早发性感音神经性听力损失和前庭功能障碍。CKO小鼠内毛细胞出现突触缺陷，表现为脑干听觉反应I波振幅下降、潜伏期延长、内毛细胞带状突触缺失、内吞区积累以及活跃区周围F-肌动蛋白网状网络缺失。CKO小鼠的耳蜗和前庭毛细胞也发生自噬通量中断和凋亡。Atp6v1c1 p.R281P敲入小鼠出现晚发性高频听力损失，毛细胞形态正常，但螺旋神经节神经元因自噬通量和凋亡中断而退化。他们的研究揭示了ATP6V1C1是一种非综合征性耳聋的阳性基因，它在毛细胞的维持和突触功能中起着重要作用。

附：英文原文

Title: ATP6V1C1 deficiency impairs auditory and vestibular hair cell function and leads to sensorineural hearing loss in humans and mice

Author: Xiuhong Pang f, Tao Yang a b c

Issue&Volume: 2026/01/13

Abstract: Multiple genes encoding v-ATPase subunits are associated with various forms of syndromic hearing loss. Their functions in hair cells, the key sensory cells required for hearing and balance, remain unclear. In this study, linkage analysis and exome sequencing of a large autosomal dominant family with non-syndromic deafness identify a pathogenic p.R281P variant in ATP6V1C1 that encodes the C1 subunit of the v-ATPase. Conditional knock-out (CKO) of Atp6v1c1 in mouse hair cells results in early-onset sensorineural hearing loss and vestibular malfunction. The CKO mice show synaptic defects in inner hair cells, evidenced by decreased wave I amplitude and prolonged latency of the auditory brainstem responses, loss of inner hair cell ribbon synapses, accumulation of endocytic compartments, and absence of F-actin mesh network surrounding the active zones. The cochlear and vestibular hair cells of the CKO mice also undergo disrupted autophagic flux and apoptosis. The Atp6v1c1 p.R281P knock-in mice develop late-onset, high-frequency hearing loss with normal hair cell morphology but degenerated spiral ganglion neurons due to disrupted autophagic flux and apoptosis. Our study reveals ATP6V1C1 as a causative gene for non-syndromic deafness and its important roles in maintenance and synaptic function of hair cells.

DOI: 10.1016/j.jgg.2026.01.005

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852726000184