Lrguk基因在精子尾部轴丝形成中的功能及机制研究

10-15% of male infertility were caused by dysspermatogenesis.Spermatogenesis is a multiple genes involved complex process, of which the etiology was still unknown. A novel testis-specfic gene named Lrguk was firstly indentified in our pre-study. It was found that point mutation of Lrguk resulted in male infertility with abnormal morphology and loss of the function of sperm tail. However, the mechanism was still need to be clarified. Based on the evidence provided above, the following hypothesis was proposed: Lrguk was a novel gene related with axoneme formation by interaction between its coded protein LRGUK with MARCH10.To confirm this, the function and mechanism of LRGUK on the sperm axoneme formation will be studied through mouse model,cilia cell line MEF and HEK293 cell line, adopting qPCR, siRNA Silenc,Western Blot,Co-Immunofluorescence, Co-Immunoprecipitation methods from animal level to gene silencing cellline model. In conclusion, we aim to illuminate the function and mechanism of Lrguk on the sperm axoneme formation and provide theoretical support for clinical diagnosis and treatment of male infertility.

10-15%的男性不育为精子发生障碍所致。精子发生是众多基因参与的复杂过程。我们在前期研究中鉴定了一个新的睾丸特异基因Lrguk，发现Lrguk点突变可导致小鼠精子尾部畸形和活力丧失进而不育，作用机制不详。本课题首次提出“Lrguk是一个精子尾部轴丝发生相关基因，其编码蛋白LRGUK可能通过与MARCH10相互作用参与精子尾部轴丝形成”的假说。为验证这一假设，本课题拟通过小鼠Lrguk突变不育模型、小鼠成纤维细胞系、HEK293细胞系等，采用qPCR、siRNA基因沉默、Western Blot、免疫共沉淀、免疫荧光共定位等手段，从动物整体水平及基因沉默细胞模型等方面探讨Lrguk在精子尾部轴丝形成中的作用及分子机制。本课题将以Lrguk基因在精子尾部轴丝发生过程中的作用机制为研究点开展研究，为临床指导男性不育的诊疗提供理论依据。