A knock-in mouse model of Pendred syndrome with Slc26a4 L236P mutation
A knock-in mouse model of Pendred syndrome with Slc26a4 L236P mutation
复制标题
Slc26a4 L236P突变的Pendred综合征敲入小鼠模型
DOI：
10.1016/j.bbrc.2019.05.157
复制
发表时间：
2019-07-23
影响因子：
3.1
通讯作者：
Gao, Jiangang
中科院分区：
文献类型：
--
作者：
Wen, Zongzhuang;Zhu, Haixia;Gao, Jiangang
SLC26A4基因突变导致Pendred综合征和非综合征性听力损失（DFNB4）。小鼠模型很好地用于研究Pendred综合征的病理学，然而，具有不同Slc26a4突变的小鼠表现出不同的表型，并且这些小鼠具有严重的耳聋和内耳畸形，这些小鼠不模仿较不严重的人类表型。在这项研究中，我们产生了一个敲入小鼠模型的Pendred综合征与Slc26a4 L236P突变，以模拟最常见的突变在人类中发现。部分L236P小鼠出现明显的前庭功能障碍，包括斜颈和绕颈，L236P小鼠出现巨大耳石和耳石膜破坏。与其他深度耳聋的Slc26a4小鼠模型不同，L236P小鼠呈现轻度至极重度听力损失，与听阈一致，内耳毛细胞也从轻微到显著损失。总之，这些数据表明，L236P小鼠表型与人类表型更相似，应用作进一步研究人类Pendred综合征的工具。(C)2019爱思唯尔公司All rights reserved.
SLC26A4 gene mutations lead to Pendred syndrome and non-syndromic hearing loss (DFNB4). The mouse model is well used to study the pathology of Pendred syndrome, however, mice with different Slc26a4 mutations exhibit different phenotypes, and these mice have severe deafness and inner ear malformations that are not imitated less severely Human phenotype. In this study, we generated a knock-in mouse model of Pendred syndrome with Slc26a4 L236P mutation to mimic the most common mutation found in human. Some L236P mice were observed to have significant vestibular dysfunction including torticollis and circling, the giant otoconia and destruction of the otoconial membrane was observed in L236P mice. Unlike other profoundly deafness in Slc26a4 mouse model, L236P mice present mild to profound hearing loss, consistent with the hearing threshold, inner ear hair cells also lost from slight to significant. Together, these data demonstrate that the L236P mouse phenotype is more similar to the human phenotype and should be used as a tool for further research into the human Pendred syndrome. (C) 2019 Elsevier Inc. All rights reserved.