耳聋是人类发病率最高的感官或功能缺陷性疾病，60%以上的耳聋与遗传有关。目前仍有众多耳聋基因未被鉴定，因此确定新的耳聋基因、揭示其致聋机制有十分重大意义。精子相关抗原6（sperm associated antigen 6，spag6）基因编码纤毛相关蛋白SPAG6，spag6的缺失导致多种疾病。我们前期研究发现，spag6在正常小鼠的内耳表达，spag6基因敲除小鼠出现重度耳聋, 但spag6导致听觉障碍的机制未见报道。本项目在前期工作的基础上，拟采用spag6基因敲除小鼠检测spag6对听功能的影响；进一步探讨spag6在平面细胞极性中的作用，检测spag6与马达蛋白的关系，分析spag6对听觉中枢发育的影响；并开展耳聋患者流行病学调查，藉此阐明spag6与听觉功能异常的关系。本项目的实施将进一步揭示听觉障碍的发生机制，为听觉功能重建提供新的理论依据和治疗靶点

Deafness represents one of the most common sensory or functional defective diseases, in which more than 60% of patients with deafness are attributed to genetic maladies. Numerous causative genes for this disorder, however, have not been identified to date. Thus, the discovery of a new pathogenic gene for a non-syndromic hearing loss and, more importantly, the elucidation of its mechanism (s) responsible for auditory dysfunction as well as reconstruction are becoming the hot spot of researches in the area of otology. Sperm associated antigen 6 (spag6) gene encodes sperm-associated antigen 6, a cilia-related protein, and the deletion of spag6 gene results in a variety of diseases. Previously, we found, for the first time, that spag6 expressed in the inner ear of wide type mice and spag6 knock out mice appeared severe hearing loss in comparison to normal subjects. The precise mechanism by which spag6 gene elicits auditory dysfunction has not been deciphered to date. Therefore, the present study was designed to: 1) test the effect of spag6 gene on auditory function utilizing spag6 knockout mice; 2) investigate the role of spag6 gene in plannar cell polarity pathway; 3) determine the relationship between spag6 and prestin; 4) analyze the impact of spag6 gene on the development of auditory center; and 5) make a genetic epidemiological survey among patients with deafness. The implementation of this project will unmask the mechanism underlying the action of spag6 gene on deafness and, in turn, offer a new theoretic framework for auditory reconstruction and, finally, may lend a novel therapeutic target for hearing loss.