Data_Sheet_12_Essential Role of CFAP53 in Sperm Flagellum Biogenesis.ZIP

The sperm flagellum is essential for male fertility. Despite vigorous research progress toward understanding the pathogenesis of flagellum-related diseases, much remains unknown about the mechanisms underlying the flagellum biogenesis itself. Here, we show that the cilia and flagella associated protein 53 (Cfap53) gene is predominantly expressed in testes, and it is essential for sperm flagellum biogenesis. The knockout of this gene resulted in complete infertility in male mice but not in the females. CFAP53 localized to the manchette and sperm tail during spermiogenesis, the knockout of this gene impaired flagellum biogenesis. Furthermore, we identified two manchette and sperm tail-associated proteins that interacted with CFAP53 during spermiogenesis. Together, our results suggest that CFAP53 is an essential protein for sperm flagellum biogenesis, and its mutations might be associated with multiple morphological abnormalities of the flagella (MMAF).

精子鞭毛（sperm flagellum）对于雄性生育能力至关重要。尽管在阐明鞭毛相关疾病的发病机制方面已取得长足研究进展，但人们对鞭毛自身生成的分子机制仍知之甚少。本研究证实，纤毛与鞭毛相关蛋白53（cilia and flagella associated protein 53，Cfap53）基因主要在睾丸组织中表达，且对精子鞭毛的生成不可或缺。该基因的敲除会导致雄性小鼠完全不育，而雌性小鼠的生育功能未受影响。在精子形成（spermiogenesis）过程中，CFAP53定位于曼切特体（manchette）与精子尾部；该基因的敲除会损害鞭毛的生成过程。此外，本研究鉴定出两种在精子形成过程中与CFAP53相互作用的曼切特体及精子尾部相关蛋白。综上，本研究结果表明CFAP53是精子鞭毛生成所必需的蛋白，其突变可能与鞭毛多形态异常（multiple morphological abnormalities of the flagella，MMAF）相关。