中心粒蛋白POC1B纯合移码突变导致少弱畸精子症的分子机制研究

少弱畸精子症（OAT）是指精子密度低、活动力减弱和畸形率增高的一类男性不育疾病。但对OAT致病的分子机制，仍知之甚少。本项目采用全外显子测序和生物信息学分析在中国近亲婚配家系所生的OAT患者中发现了POC1B纯合移码突变（c.151delG），并制备了携带该突变的小鼠模型。POC1B是中心体的重要组成成分，在中心体组装和稳定性维持等过程发挥重要作用。初步研究结果提示该突变导致POC1B表达异常，且携带POC1B纯合突变的雄性小鼠不育，精液中精子密度降低，畸形率增加。因此我们推测：POC1B突变影响精子发生及鞭毛发育过程导致少弱畸精子症。为此，本项目拟开展以下工作：1.深入研究该突变对POC1B表达定位及中心体功能的影响；2.深入研究该突变在精子发生的具体作用；3.探讨突变导致精子发生及鞭毛发育异常的分子机制。以期证实POC1B突变是导致人类少弱畸精子症的致病原因，揭示其致病机制。

oligoasthenoteratozoospermia (OAT), has been reported as combination of abnormalities in these three semen parameters (low sperm count，decreased sperm motility and increased deformity rate). OAT is a common cause of male infertility. Its molecular mechanism is needed to be elucidated. However, little is known about the molecular mechanism of OAT. In this project, POC1B homozygous frameshift mutation (c.151delG) was found in a Chinese consanguineous family with OAT patients by whole exon sequencing. The preliminary results suggest that the mutation leads to the production of POC1B truncated protein in patients, and the male mice carrying human mutation are infertile, the number of sperm in semen decreases and the rate of deformity increases. Therefore, we speculate that POC1B mutation affects the process of sperm maturation and leads to OAT. To prove this: 1. in-depth study of the impact of this mutation on the expression and localization of POC1B. 2. we will try to intensively study the specific role of the mutation in spermatogenesis. 3. explore the molecular mechanism of this mutation on abnormal spermatogenesis and flagella development. Based on these studies, we will elucidate the mechanism of oligoasthenoteratozoospermia caused by POC1B mutation.