Department of Otolaryngology, University of Kentucky Medical School, Lexington, KY 40536, USA.
Neurosci Lett. 2012 Oct 18;528(1):36-41. doi: 10.1016/j.neulet.2012.08.085. Epub 2012 Sep 11.
Connexin26 (Cx26, GJB2) mutations can induce congenital deafness and are responsible for ∼50% of nonsyndromic hearing loss in children. Mouse models show that Cx26 deficiency induces cochlear development disorder, hair cell loss, and spiral ganglion (SG) neuron degeneration. Hair cell loss and cell degeneration have been considered as a primary causer responsible for Cx26 deficiency associated hearing loss. In this study, by coincidental examination of cochlear postnatal development with recording of auditory brainstem response (ABR) and hair cell function, we found that occurrence of hearing loss in Cx26 knockout (KO) mice was ahead of hair cell loss and cochlear cell degeneration. ABR was absent at the whole-frequency range (8-40 kHz) after birth. However, cochlear cells including SG neurons had no significant degeneration throughout postnatal development. Severe cochlear hair cell loss and SG neuron degeneration were only visible in middle and basal turns, i.e., in middle and high frequency regions, in the adult Cx26 KO mouse cochlea. Functional tests show that hair cells in Cx26 KO mice functioned normally; outer hair cells retained electromotility. These data suggest that cell degeneration is not a primary causer of Cx26 deficiency associated hearing loss. Some mechanisms other than cell degeneration, such as cochlear development disorders, may play an essential role in this common hereditary deafness.
间隙连接蛋白 26（Cx26，GJB2）突变可引起先天性耳聋，是儿童非综合征性听力损失的主要原因之一，约占 50%。小鼠模型表明，Cx26 缺失可诱导耳蜗发育障碍、毛细胞缺失和螺旋神经节（SG）神经元变性。毛细胞缺失和细胞变性被认为是 Cx26 缺乏相关听力损失的主要原因。在这项研究中，我们通过对 Cx26 敲除（KO）小鼠耳蜗出生后发育的偶然检查，以及听觉脑干反应（ABR）和毛细胞功能的记录，发现 Cx26 KO 小鼠听力损失的发生早于毛细胞缺失和耳蜗细胞变性。出生后整个频率范围（8-40 kHz）的 ABR 均缺失。然而，在整个出生后发育过程中，包括 SG 神经元在内的耳蜗细胞均无明显变性。严重的耳蜗毛细胞缺失和 SG 神经元变性仅见于中、底回，即在成年 Cx26 KO 小鼠耳蜗的中、高频区。功能测试表明 Cx26 KO 小鼠的毛细胞功能正常；外毛细胞保留了电动力。这些数据表明，细胞变性不是 Cx26 缺乏相关听力损失的主要原因。除细胞变性外，某些机制，如耳蜗发育障碍，可能在这种常见的遗传性耳聋中起重要作用。
