University of Western Ontario, Department of Anatomy and Cell Biology, London, Ontario, Canada, N6A 5C1.
University of Western Ontario, Department of Anatomy and Cell Biology, London, Ontario, Canada, N6A 5C1
J Cell Sci. 2018 May 4;131(9):jcs214635. doi: 10.1242/jcs.214635.
Given the importance of connexin43 (Cx43, encoded by ) function in the central nervous system and sensory organ processing, we proposed that it would also be crucial in auditory function. To that end, hearing was examined in two mouse models of oculodentodigital dysplasia that globally express mutations resulting in mild or severe loss of Cx43 function. Although Cx43 mutant mice, with ∼50% Cx43 channel function, did not have any hearing loss, Cx43 mutant mice, with ∼20% Cx43 channel function, had severe hearing loss. There was no evidence of inner ear sensory hair cell loss, suggesting that the mechanism for Cx43-linked hearing loss lies downstream in the auditory pathway. Since evidence suggests that Cx26 function is essential for hearing and may be protective against noise-induced hearing loss, we challenged Cx43 mice with a loud noise and found that they had a similar susceptibility to noise-induced hearing loss to that found in controls, suggesting that decreased Cx43 function does not sensitize the mice for environmentally induced hearing loss. Taken together, this study suggests that Cx43 plays an important role in baseline hearing and is essential for auditory processing.This article has an associated First Person interview with the first author of the paper.
鉴于连接蛋白 43（Cx43，由 编码）在中枢神经系统和感觉器官处理中的功能重要性，我们推测它在听觉功能中也至关重要。为此，我们在两种眼-牙-指发育不良的小鼠模型中检查了听力，这些模型全局表达导致 Cx43 功能轻度或严重丧失的 突变。尽管 Cx43 突变小鼠的 Cx43 通道功能约为 50%，但它们没有任何听力损失，而 Cx43 突变小鼠的 Cx43 通道功能约为 20%，则存在严重的听力损失。没有内耳感觉毛细胞缺失的证据，这表明 Cx43 相关性听力损失的机制位于听觉通路的下游。由于有证据表明 Cx26 功能对于听力至关重要，并且可能对噪声性听力损失具有保护作用，因此我们用强噪声对 Cx43 小鼠进行了挑战，发现它们对噪声性听力损失的易感性与对照组相似，这表明 Cx43 功能的降低并不会使小鼠对环境引起的听力损失敏感。综上所述，本研究表明 Cx43 在基础听力中发挥重要作用，并且是听觉处理所必需的。本文有该论文第一作者的相关第一人称采访。
