Reduced Connexin26 in the Mature Cochlea Increases Susceptibility to Noise-Induced Hearing Lossin Mice.
Reduced Connexin26 in the Mature Cochlea Increases Susceptibility to Noise-Induced Hearing Lossin Mice.
复制标题
成熟耳蜗中连接蛋白26的减少会增加小鼠对噪音引起的听力损失的敏感性
DOI：
10.3390/ijms17030301
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发表时间：
2016-02-26
影响因子：
5.6
通讯作者：
Kong WJ
中科院分区：
文献类型：
--
作者：
Zhou XX;Chen S;Xie L;Ji YZ;Wu X;Wang WW;Yang Q;Yu JT;Sun Y;Lin X;Kong WJ
连接蛋白26（Cx26，由GJB2编码）突变是导致非综合征性耳聋最常见的原因。人们认为GJB2与噪声性听力损失（NIHL）有关。然而，Cx26在噪声性听力损失中所起的作用仍不明确。为探究Cx26与噪声性听力损失之间的关联，我们通过在出生后第18天（P18）条件性敲低Cx26，建立了Cx26基因敲低（KD）小鼠模型，随后观察了这些小鼠在有或无噪声暴露情况下的听阈及形态学变化。Cx26基因敲低小鼠未出现明显的听力损失和毛细胞退化，而遭受声损伤的Cx26基因敲低小鼠，相比仅暴露于噪声的同窝小鼠，听力损失更严重，且几乎没有恢复。此外，噪声暴露后，在Cx26基因敲低小鼠中观察到广泛的外毛细胞缺失以及柯蒂氏器底部更严重的破坏。这些数据表明，成熟小鼠耳蜗中Cx26表达的降低，可能会增加对噪声性听力损失的易感性，并加速柯蒂氏器中的细胞退化。
Connexin26 (Cx26, encoded by GJB2) mutations are the most common cause of non-syndromic deafness. GJB2 is thought to be involved in noise-induced hearing loss (NIHL). However, the role of Cx26 in NIHL is still obscure. To explore the association between Cx26 and NIHL, we established a Cx26 knockdown (KD) mouse model by conditional knockdown of Cx26 at postnatal day 18 (P18), and then we observed the auditory threshold and morphologic changes in these mice with or without noise exposure. The Cx26 KD mice did not exhibit substantial hearing loss and hair cell degeneration, while the Cx26 KD mice with acoustic trauma experienced higher hearing loss than simple noise exposure siblings and nearly had no recovery. Additionally, extensive outer hair cell loss and more severe destruction of the basal organ of Corti were observed in Cx26 KD mice after noise exposure. These data indicate that reduced Cx26 expression in the mature mouse cochlea may increase susceptibility to noise-induced hearing loss and facilitate the cell degeneration in the organ of Corti.