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.

GJB2基因突变是常染色体隐性遗传非综合征性遗传性耳聋的最常见原因。对于患有严重至极重度GJB2相关耳聋的患者来说，人工耳蜗已成为改善听力的唯一疗法。先前的一些研究强调了保留耳蜗神经组件对于在人工耳蜗植入后获得良好结果的关键作用。因此，我们生成了条件敲除小鼠模型（Cx26-CKO），其中由 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毛细胞和Deiter细胞的大量损失，这代表了GJB2基因突变引起的人类耳聋的极端形式。此外，Cx26-CKO小鼠的周围听觉神经系统还发现多种病理变化，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节破坏。这些发现为 Cx26 缺失小鼠的耳聋机制和重度耳聋的治疗提供了宝贵的见解。