E3泛素连接酶参与调控多种生理过程，在精子变形阶段发挥了重要的调控作用。目前很多畸形精子症的遗传原因尚不能被已知致病基因解释。申请人发现E3泛素连接酶Fbxo24在人类和小鼠中存在高度保守性，且在睾丸组织中呈特异性表达。Fbxo24敲除会导致雄性小鼠完全不育，精子总数减少，出现大量的畸形精子，表现为精子头部去浓缩和精子尾部中段缺陷，提示Fbxo24参与调控了精子变形过程。本课题拟进一步分离敲除小鼠的圆形精子和延长形精子，筛选与Fbxo24的互作蛋白进而发现其底物蛋白，结合蛋白组学等方法揭示其参与的信号通路，分析组蛋白-鱼精蛋白替换和拟染色小体组成、运输方面的变化，从而阐明Fbxo24缺失导致精子不能正常发育的机理。本项目旨在利用小鼠模型探索Fbxo24的生物学功能和参与精子变形的分子机制，为由遗传因素导致人类畸形精子症的诊治提供新的理论依据。

E3 ubiquitin ligase regulates a variety of physiological processes, which plays an important regulatory role in the process of spermiogenesis. At present, the genetic causes of many teratozoospermia cannot be explained by known disease-causing gene. We previously found that E3 ubiquitin ligase Fbxo24 was highly conserved in both human and mouse, and specially expressed in the testis. Fbxo24 knockout mouse can lead to complete sterility of male mice, which have reduced sperm count and a large number of abnormal sperm, showing defective condensation of sperm head and mid piece of sperm tail, indicating that Fbxo24 is involved in regulating spermiogenesis. This project intends to screen Fbxo24 interacted proteins and further found the substrate protein from the isolated the round spermatids and elongated spermatids, reveal Fbxo24 involved signaling pathway by proteinomics, and analyze the changes in histone to protamine transition and composition and transportation of chromatid body, which will elucidate the cause of failure normal sperm development in Fbxo24 knockout mice. This project aims to explore the biological function and molecular mechanism of Fbxo24 involved in spermiogenesis, and to provide a new theoretical evidence for the diagnosis and treatment of human teratozoospermia caused by genetic factors.