POSTNATAL DEVELOPMENT OF THE ORGAN OF CORTI IN DOMINANT-NEGATIVE GJB2 TRANSGENIC MICE
POSTNATAL DEVELOPMENT OF THE ORGAN OF CORTI IN DOMINANT-NEGATIVE GJB2 TRANSGENIC MICE
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DOI：
10.1016/j.neuroscience.2008.08.027
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发表时间：
2008-10-28
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：
Inoshita, A.;Iizuka, T.;Ikeda, K.
遗传性听力损失是最常见的遗传性人类出生缺陷之一，2000年就有一例。先天性双侧非综合征性感音神经性耳聋病例中有相当高的比例（50%）与编码连接蛋白的GJB 2突变有关26。据推测，耳蜗中的缝隙连接，特别是连接蛋白26，提供了一个细胞间通道，通过该通道K+被转运以维持高水平的耳蜗内电位，这对感觉毛细胞的兴奋至关重要。我们先前报道了一种携带人连接蛋白26 R75 W突变的小鼠模型（R75 W+小鼠）的产生。本研究试图评估出生后Corti器官在R75 W+小鼠中的发育。R75 W+小鼠在出生后的整个发育过程中从未显示出听觉脑干反应波形，表明听觉器官发育障碍。出生后（P）5-14天的组织学观察结果的特征是：I）没有Corti隧道、Nuel间隙或外毛细胞周围的空间，ii）内柱细胞中微管数量显著减少，iii）Corti器官高度缩短，iv）Corti器官细胞横截面积增加。因此，形态学观察证实，显性阴性Gjb 2突变显示耳蜗支持细胞发育不完全。另一方面，感觉毛细胞的发育，至少从P5到P12，没有受到影响。本研究表明，Gjb 2是必不可少的出生后发育的Corti器官和正常的听力。(C)2008年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Hereditary hearing loss is one of the most prevalent inherited human birth defects, affecting one in 2000. A strikingly high proportion (50%) of congenital bilateral nonsyndromic sensorineural deafness cases have been linked to mutations in the GJB2 coding for the connexin26. It has been hypothesized that gap junctions in the cochlea, especially connexin26, provide an intercellular passage by which K+ are transported to maintain high levels of the endocochlear potential essential for sensory hair cell excitation. We previously reported the generation of a mouse model carrying human connexin26 with R75W mutation (R75W+ mice). The present study attempted to evaluate postnatal development of the organ of Corti in the R75W+ mice. R75W+ mice have never shown auditory brainstem response waveforms throughout postnatal development, indicating the disturbance of auditory organ development. Histological observations at postnatal days (P) 5-14 were characterized by I) absence of tunnel of Corti, Nuel's space, or spaces surrounding the outer hair cells, ii) significantly small numbers of microtubules in inner pillar cells, iii) shortening of height of the organ of Corti, and iv) increase of the cross-sectional area of the cells of the organ of Corti. Thus, morphological observations confirmed that a dominant-negative Gjb2 mutation showed incomplete development of the cochlear supporting cells. On the other hand, the development of the sensory hair cells, at least from P5 to P12, was not affected. The present study suggests that Gjb2 is indispensable in the postnatal development of the organ of Corti and normal hearing. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.