近日，华中科技大学Yu Sun等研究人员合作发现，螺旋神经节神经元的异常神经支配、脱髓鞘和变性以及半结的破坏与Cx26缺失小鼠耳聋的发生有关。2024年2月4日，《神经科学通报》在线发表了这项成果。

研究人员产生了一种条件性基因敲除小鼠模型（Cx26-CKO），在该模型中，Sox2启动子驱动的耳蜗支持细胞中的Cx26被完全删除。Cx26-CKO小鼠表现出严重的听力损失以及大量毛细胞和Deiter细胞的缺失，这代表了由GJB2基因突变引起的人类耳聋的极端形式。

此外，Cx26-CKO小鼠的外周听觉神经系统也出现了多种病理变化，包括神经支配异常、脱髓鞘、螺旋神经节神经元变性以及半结中断。这些发现为研究Cx26缺失小鼠的耳聋机制和治疗严重耳聋提供了宝贵的见解。

据了解，GJB2基因突变是导致常染色体隐性非综合征遗传性耳聋的最常见原因。对于患有重度到极重度GJB2相关性耳聋的患者，人工耳蜗已成为改善听力的唯一治疗方法。之前的一些研究强调了保留人工耳蜗神经元对人工耳蜗植入术后取得良好效果的关键作用。

附：英文原文

Title: Abnormal Innervation, Demyelination, and Degeneration of Spiral Ganglion Neurons as Well as Disruption of Heminodes are Involved in the Onset of Deafness in Cx26 Null Mice

Author: Qiu, Yue, Xie, Le, Wang, Xiaohui, Xu, Kai, Bai, Xue, Chen, Sen, Sun, Yu

Issue&Volume: 2024-02-04

Abstract: GJB2 gene mutations are the most common causes of autosomal recessive non-syndromic hereditary deafness. For individuals suffering from severe to profound GJB2-related deafness, cochlear implants have emerged as the sole remedy for auditory improvement. Some previous studies have highlighted the crucial role of preserving cochlear neural components in achieving favorable outcomes after cochlear implantation. Thus, we generated a conditional knockout mouse model (Cx26-CKO) in which Cx26 was completely deleted in the cochlear supporting cells driven by the Sox2 promoter. The Cx26-CKO mice showed severe hearing loss and massive loss of hair cells and Deiter’s cells, which represented the extreme form of human deafness caused by GJB2 gene mutations. In addition, multiple pathological changes in the peripheral auditory nervous system were found, including abnormal innervation, demyelination, and degeneration of spiral ganglion neurons as well as disruption of heminodes in Cx26-CKO mice. These findings provide invaluable insights into the deafness mechanism and the treatment for severe deafness in Cx26-null mice.

DOI: 10.1007/s12264-023-01167-x

Source: https://link.springer.com/article/10.1007/s12264-023-01167-x