Connexin30 null and conditional connexin26 null mice display distinct pattern and time course of cellular degeneration in the cochlea.
Connexin30 null and conditional connexin26 null mice display distinct pattern and time course of cellular degeneration in the cochlea.
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DOI：
10.1002/cne.22117
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发表时间：
2009-10-20
期刊：
影响因子：
--
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Sun Y;Tang W;Chang Q;Wang Y;Kong W;Lin X
连接蛋白26（Cx26）和Cx30的突变是人类非综合征型遗传性耳聋的最常见原因。为了了解潜在的分子机制，我们研究了条件性Cx26（cCx26）null和Cx30 null小鼠耳蜗细胞变性的模式和时间过程。在cCx26基因敲除小鼠中，出生后第14天左右观察到外毛细胞（OHC）和OHC周围支持细胞的初始变性。生后1个月，Corti中回器细胞全部丧失，并逐渐向基回和顶回扩散。大多数螺旋神经节（SG）的神经元在中间和基底回消失，在前三个月，而大量的顶端SG神经元存活。在Cx30缺失小鼠的耳蜗中，观察到大多数内部HC、支持细胞和SG神经元的存活长达18个月。SG顶神经元和OHC变性最严重。OHC丢失遵循缓慢的时间过程和从基底到心尖的梯度。在光学显微镜水平观察到的内淋巴间隙和血管纹的大体结构在两种Cx缺失小鼠模型中均无变化。这项研究表明，cCx26基因敲除小鼠耳蜗中的细胞变性比Cx30基因敲除小鼠中观察到的细胞变性明显更快和更广泛。尽管Cx26和Cx30在耳蜗缝隙连接形成中共同组装，但cCx26和Cx30缺失小鼠显示的根本不同的发病过程表明潜在的耳聋机制是异质的。
Mutations in connexin26 (Cx26) and Cx30 are the most common cause of non-syndromic inherited deafness in humans. To understand underlying molecular mechanisms, we investigated the pattern and time course of cellular degeneration in the cochlea of conditional Cx26 (cCx26) null and Cx30 null mice. In cCx26 null mice, initial degeneration was observed around postnatal day 14 in outer hair cells (OHCs) and supporting cells surrounding the OHCs. All cells in the middle turn organ of Corti were lost one month after birth and degeneration gradually spread to the basal and apical turns. Most spiral ganglion (SG) neurons in the middle and basal turns disappeared in the first three months, while significant amounts of apical SG neurons survived. In the cochlea of Cx30 null mice, survival of most inner HCs, supporting cells and SG neurons was observed for up to eighteen months. The most severe degeneration was found in apical SG neurons and OHCs. OHC loss followed a slow time course and a base to apex gradient. Gross structures of the endolymphatic space and stria vascularis observed at the light microscope level were unchanged in either Cx null mouse models. This study revealed that cellular degeneration in the cochlea of cCx26 null mice was dramatically more rapid and widespread than that observed in Cx30 null mice. The radically different pathogenesis processes displayed by cCx26 and Cx30 null mice suggest heterogeneous underlying deafness mechanisms, despite of the coassembly of Cx26 and Cx30 in forming gap junctions in the cochlea.
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