COCHLEAR OUTER HAIR CELLS IN A DOMINANT-NEGATIVE CONNEXIN26 MUTANT MOUSE PRESERVE NON-LINEAR CAPACITANCE IN SPITE OF IMPAIRED DISTORTION PRODUCT OTOACOUSTIC EMISSION
COCHLEAR OUTER HAIR CELLS IN A DOMINANT-NEGATIVE CONNEXIN26 MUTANT MOUSE PRESERVE NON-LINEAR CAPACITANCE IN SPITE OF IMPAIRED DISTORTION PRODUCT OTOACOUSTIC EMISSION
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DOI：
10.1016/j.neuroscience.2009.08.043
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发表时间：
2009-12-15
期刊：
影响因子：
3.3
通讯作者：
Ikeda, K.
中科院分区：
文献类型：
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作者：
Minekawa, A.;Abe, T.;Ikeda, K.
连接蛋白26基因（GJB2）中的突变是先天性双侧非伴奏感官听力损失的最常见遗传原因。转基因小鼠的携带携带人CX26具有R75W突变，该突变已在具有常染色体显性负遗传的聋子家族中被鉴定出来[Kudo T等。 （2003）Hum Mol Genet 12：9951004]。显性阴性的GJB2 R75W转基因小鼠模型显示出耳蜗支撑细胞的不完整发展，从而导致出生后的聋哑[Inoshita A等。 （2008）神经科学156：1039-1047]。 GJB2 R75W转基因小鼠中的CX26缺陷仅限于支撑细胞。目前尚不清楚尽管存在外毛细胞（OHC），但为什么听觉反应受到严重干扰。本研究旨在评估OHC体内和体外功能的发育变化，以及R75W转基因小鼠中OHC和相邻支持细胞的精细结构。在整个发育过程中，R75W转基因小鼠的任何频率均未观察到可检测到的失真产物。在这些小鼠中观察到的一个特征表型是Corti的隧道，Nuel的空间和OHC周围的空间的缺失。 OHC被周围的支撑细胞压缩并挤压。另一方面，OHC正常发展。侧壁的结构特征，例如质膜下方的膜结合的地下库斯特纳完整。 Prestin是电压依赖性运动蛋白，通过免疫组织化学观察到转基因和非转基因小鼠的OHC基底外侧膜中。在转基因小鼠和对照小鼠之间，在发育过程中分离的OHC在发育过程中没有显着差异。本研究表明，在OHC的适当细胞功能中，支持细胞的正常发育是必不可少的。 （c）2009 IBRO。由Elsevier Ltd.出版。保留所有权利。
Mutations in the connexin26 gene (GJB2) are the most common genetic cause of congenital bilateral non-syndromic sensorineural hearing loss. Transgenic mice were established carrying human Cx26 with the R75W mutation that was identified in a deaf family with autosomal dominant negative inheritance [Kudo T et al. (2003) Hum Mol Genet 12:9951004]. A dominant-negative Gjb2 R75W transgenic mouse model shows incomplete development of the cochlear supporting cells, resulting in profound deafness from birth [Inoshita A et al. (2008) Neuroscience 156:1039-1047]. The Cx26 defect in the Gjb2 R75W transgenic mouse is restricted to the supporting cells; it is unclear why the auditory response is severely disturbed in spite of the presence of outer hair cells (OHCs). The present study was designed to evaluate developmental changes in the in vivo and in vitro function of the OHC, and the fine structure of the OHC and adjacent supporting cells in the R75W transgenic mouse. No detectable distortion product oto-acoustic emissions were observed at any frequencies in R75W transgenic mice throughout development. A characteristic phenotype observed in these mice was the absence of the tunnel of Corti, Nuel's space, and spaces surrounding the OHC; the OHC were compressed and squeezed by the surrounding supporting cells. On the other hand, the OHC developed normally. Structural features of the lateral wall, such as the membrane-bound subsurface cisterna beneath the plasma membrane, were intact. Prestin, the voltage-dependent motor protein, was observed by immunohistochemistry in the OHC basolateral membranes of both transgenic and non-transgenic mice. No significant differences in electromotility of isolated OHCs during development was observed between transgenic and control mice. The present study indicates that normal development of the supporting cells is indispensable for proper cellular function of the OHC. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.