睾丸特异性蛋白Tulp2在精子形成异常中的作用及机制研究

Tulp家族成员缺失或突变可导致多种纤毛病变性疾病，Tulp2是Tulp基因家族中睾丸特异性表达成员，羧基端含有保守的tubby结构域，氨基端含有IFT-A结合结构域，但其功能未明。项目组前期研究发现，Tulp2主要表达于精子细胞胞质，其基因敲除小鼠雄性不育，表现为少弱畸精子症，同时Tulp2能与伴侣蛋白复合体CCT亚基CCT8相互作用。为探索Tulp2在精子形成异常中的作用及机制，本项目拟从以下四个方面开展研究：（1）深入分析Tulp2基因敲除小鼠，明确精子形成异常表型；（2）研究Tulp2在精子形成过程中的具体作用；（3）研究Tulp2在精子形成中的分子作用机制，揭示其如何与CCT8相互作用调控精子形成过程；（4）验证Tulp2与临床少弱畸精子症之间的相关性。这些研究将阐明Tulp2缺失所致少弱畸精子症的发病机制，为男性不育症的临床诊断及治疗提供理论基础和新的靶标。

Mutations or deletions in the Tulp genes are associated with ciliopathy disorder. Tulp2, the only testis-specific member of Tulp family, contains highly conserved signature carboxy-terminal tubby domain and intraflagellar transport A binding domain in the amino termini. But its function has not been illuminated till now. In previous study, we found that Tulp2 dominantly expressed in the cytoplasm of spermatid. Tulp2-deficient males with oligoasthenoteratozoospermia were completely infertile. And Tulp2 can interact with CCT subunit theta (CCT8). To investigate the function and molecular mechanism of Tulp2 in impaired spermiogenesis, studies will be carried out from the following four aspects: (1) Phenotype analysis of Tulp2 knockout mice. (2) Analysis the roles of Tulp2 in spermiogenesis. (3) Analysis the molecular mechanism of Tulp2 by interacting with CCT8 in spermiogenesis. (4) Analysis the correlation of Tulp2 with male infertility. The above series of studies will help us reveal the pathogenesis of oligoasthenoteratozoospermia resulting from Tulp2 disruption. These studies will also provide a theoretical basis and practical possibility for the diagnosis and treatment of male infertility.