Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise.
Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise.
复制标题
DOI：
10.1126/sciadv.adf4144
复制
发表时间：
2023-02-10
期刊：
影响因子：
13.6
通讯作者：
Zhao, Hong -Bo
中科院分区：
文献类型：
--
作者：
Liu, Li -Man;Liang, Chun;Chen, Jin;Fang, Shu;Zhao, Hong -Bo
缝隙连接基因GJB2(Cx26)突变导致50%的非综合征性听力损失。无耳聋的隐性杂合突变携带者约占总人口的10%~20%。在这里，我们报告了一个意想不到的发现，这些杂合子携带者有听力过敏症，活跃的耳蜗放大增加。小鼠模型显示，Cx26基因的杂合缺失减少了耳蜗侧壁内电位的产生，并导致外毛细胞电动运动蛋白prestin代偿性上调，从而增加了耳蜗的主动放大和听力敏感性。主动耳蜗放大度的增加也增加了对噪声的敏感性；暴露在日常水平的噪声中会导致Cx26+/−小鼠永久性听力阈值漂移，导致听力损失。这项研究表明，Cx26隐性杂合突变并不像以前认为的那样对听力无害，并可能导致类似听力过敏症的听力过敏症。数据还表明，GJB2异源突变携带者对噪声易感，在日常生活中应避免噪声暴露。Cx26杂合突变并不是无害的；它们会导致听力过度敏感，并增加对噪音的敏感性。
Gap junction gene GJB2 (Cx26) mutations cause >50% of nonsyndromic hearing loss. Its recessive hetero-mutation carriers, who have no deafness, occupy ~10 to 20% of the general population. Here, we report an unexpected finding that these heterozygote carriers have hearing oversensitivity, and active cochlear amplification increased. Mouse models show that Cx26 hetero-deletion reduced endocochlear potential generation in the cochlear lateral wall and caused outer hair cell electromotor protein prestin compensatively up-regulated to increase active cochlear amplification and hearing sensitivity. The increase of active cochlear amplification also increased sensitivity to noise; exposure to daily-level noise could cause Cx26+/− mice permanent hearing threshold shift, leading to hearing loss. This study demonstrates that Cx26 recessive heterozygous mutations are not “harmless” for hearing as previously considered and can cause hyperacusis-like hearing oversensitivity. The data also indicate that GJB2 hetero-mutation carriers are vulnerable to noise and should avoid noise exposure in daily life. Cx26 hetero-mutations are not harmless; they can cause hearing over-sensitivity and increase susceptibility to noise.
登录
查看更多内容
影响因子：
4
作者：
del Castillo, FJ;Rodríguez-Ballesteros, M;del Castillo, I
通讯作者：
del Castillo, I
影响因子：
2.5
作者：
Huang, ZW;Luo, YY;Zhao, HB
通讯作者：
Zhao, HB
影响因子：
8.8
作者：
Chan, Dylan K.;Schrijver, Iris;Chang, Kay W.
通讯作者：
Chang, Kay W.
DOI：
10.1007/bf00186783
发表时间：
1995-02-01
期刊：
ANATOMY AND EMBRYOLOGY
影响因子：
--
作者：
KIKUCHI, T;KIMURA, RS;ADAMS, JC
通讯作者：
ADAMS, JC
影响因子：
3.5
作者：
Han, Sung-Hee;Park, Hong-Joon;Lee, Kyoung-Ryul
通讯作者：
Lee, Kyoung-Ryul