Establishment and characterization of mouse models for hearing loss based on Molecular interaction

为了建立新的小鼠耳聋模型并明确其听力损害的分子机制，我们开展了位置克隆、内耳毛细胞表达分析和耳聋相关蛋白之间的蛋白质相互作用研究。1)我们确定了两个新的自发突变的致病基因为肌球蛋白VI。2)4.1B和明胶蛋白可能是肌球蛋白XV-惠林复合体的成员，该复合体对立体纤毛的成熟起重要作用。3)SANS和Whrlin突变体的双纯合子表型数据表明，SANS的功能与WHRLIN相互作用，平面细胞极性在毛细胞立体纤毛中的相互作用发挥规律。

To establish new mouse models for deafness and identify molecular mechanism of hearing impairment, we carried out positional cloning approach, expression analysis of the inner ear hair cells and protein-protein interaction studies among the deafness associated-proteins. 1) We identified that responsible gene of two new spontaneous mutants is myosin VI. 2) 4.1B and gelsolin may be members of the myosin XV-whirlin complex that is important for stereocilia maturation. 3) Phenotypic data of double homozygotes between Sans and Whrlin mutants suggest that the function of SANS interacts with WHRLIN and the interaction play regulation of planar cell polarity in stereocilia of the hair cells.