Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31
Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31
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DOI：
10.1038/ng1208
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发表时间：
2003-08-01
期刊：
影响因子：
30.8
通讯作者：
Brown, SDM
中科院分区：
文献类型：
--
作者：
Mburu, P;Mustapha, M;Brown, SDM
旋转小鼠突变体（wi）对声音刺激没有反应，对内耳柯蒂氏器感觉毛细胞的详细超微结构分析表明，旋转基因编码一种参与内毛细胞（IHC）和外毛细胞（OHC）静纤毛伸长和维持的蛋白质。 BAC介导的小鼠表型转基因校正和突变分析确定了致病基因编码一种名为whirlin的新型PDZ蛋白。编码 Whirlin 的基因也是人类常染色体隐性耳聋基因座 DFNB31 的基础。在小鼠耳蜗中，whirlin 在感觉 IHC 和 OHC 静纤毛中表达。我们的研究结果表明，这种新型包含 PDZ 结构域的分子充当膜下分子复合物的组织者，控制协调的肌动蛋白聚合和静纤毛的膜生长。
The whirler mouse mutant (wi) does not respond to sound stimuli, and detailed ultrastructural analysis of sensory hair cells in the organ of Corti of the inner ear indicates that the whirler gene encodes a protein involved in the elongation and maintenance of stereocilia in both inner hair cells (IHCs) and outer hair cells (OHCs). BAC-mediated transgene correction of the mouse phenotype and mutation analysis identified the causative gene as encoding a novel PDZ protein called whirlin. The gene encoding whirlin also underlies the human autosomal recessive deafness locus DFNB31. In the mouse cochlea, whirlin is expressed in the sensory IHC and OHC stereocilia. Our findings suggest that this novel PDZ domain containing molecule acts as an organizer of submembranous molecular complexes that control the coordinated actin polymerization and membrane growth of stereocilia.