Increased susceptibility to acoustic trauma in a mouse model of non‐syndromic sensorineural deafness, DFNB91,European Journal of Neuroscience

当前位置： X-MOL 学术 › Eur. J. Neurosci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Increased susceptibility to acoustic trauma in a mouse model of non‐syndromic sensorineural deafness, DFNB91
European Journal of Neuroscience ( IF 2.7 ) Pub Date : 2020-10-19 , DOI: 10.1111/ejn.15011
Justin Tan ₁ , Dion Kaiserman ₂ , Stephen J O'Leary ₁ , Phillip I Bird ₂

Affiliation

Inactivating mutations of SERPINB6 in humans result in progressive hearing loss starting in early adulthood (DFNB91). We have previously shown that C57BL/6J mice lacking the orthologous gene, Serpinb6a, exhibit progressive hearing loss, which is associated with progressive loss of distinct cell types in the organ of Corti beginning with outer hair cells (OHCs). However, deafness in these animals occurs much earlier than expected, possibly because C57BL/6J mice also carry an age‐related hearing loss mutation in the cadherin 23 gene (Cdh23^ahl) that causes late onset hearing loss. The CBA/CaH strain of mice does not carry Cdh23^ah/ahl and may represent a better model of the human DFNB91 patients. Here, we show that transfer of the mutant Serpinb6a allele onto the Cdh23 normal CBA/CaH background markedly delays onset of hearing loss, more closely phenocopying DFNB91, without altering the pattern of cellular loss. Young, pre‐symptomatic mice of this genotype exposed to acoustic trauma exhibit permanent hearing loss, compared to controls, associated with the disappearance of OHCs. We conclude that Serpinb6 helps to maintain hearing by protecting hair cells from stress.

中文翻译：

在非综合征性感音神经性耳聋DFNB91小鼠模型中对听觉创伤的敏感性增加

人体内SERPINB6的失活突变导致成年早期开始逐渐进行性听力丧失（DFNB91）。我们以前已经表明，缺少直系同源基因Serpinb6a的C57BL / 6J小鼠表现出进行性听力丧失，这与从外毛细胞（OHC）开始的Corti器官中不同细胞类型的进行性丧失有关。但是，这些动物的耳聋发生时间比预期的要早得多，这可能是因为C57BL / 6J小鼠还在钙粘蛋白23基因（Cdh23 ^ahl）中携带了与年龄相关的听力损失突变，从而导致迟发性听力损失。小鼠的CBA / CaH株不携带Cdh23 ^{ah / ahl}并可能代表人类DFNB91患者的更好模型。在这里，我们显示突变体Serpinb6a等位基因转移到Cdh23正常CBA / CaH背景上显着延迟了听力损失的发作，更紧密地复制DFNB91，而没有改变细胞损失的模式。与对照组相比，这种基因型暴露于听觉创伤的年轻，有症状的小鼠表现出永久性听力丧失，与OHC的消失有关。我们得出结论，Serpinb6通过保护毛细胞免受压力来帮助维持听力。

更新日期：2020-10-19

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11