Loss of Axdnd1 causes sterility due to impaired spermatid differentiation in mice

[摘要] Purpose Spermiogenesis, the process of deformation of sperm head morphology and flagella formation, is a phenomenon unique to sperm. Axonemal dynein light chain proteins are localized to sperm flagella and are known to be involved in sperm motility. Here, we focused on the gene axonemal dynein light chain domain containing 1 ( Axdnd1 ) with the aim to determine the function of its protein product AXDND1. Methods To elucidate the role of AXDND1 in spermatogenesis, we generated Axdnd1  knockout (KO) mice using the CRISPR/Cas9 system. The generated mice were subjected to fertility tests and analyzed by immunohistochemistry. Result The Axdnd1  KO mouse exhibited sterility caused by impaired spermiogenesis during the elongation step as well as abnormal nuclear shaping and manchette, which are essential for spermiogenesis. Moreover, AXDND1 showed enriched testicular expression and was localized from the mid-pachytene spermatocytes to the early spermatids. Conclusion Axdnd1 is essential for spermatogenesis in the mouse testes. These findings improve our understanding of spermiogenesis and related defects. According to a recent report, deleterious heterozygous mutations in AXDND1 were found in non-obstructive azoospermia (NOA) patients. Therefore, Axdnd1  KO mice could be used as a model system for NOA, which will greatly contribute to future NOA treatment studies.

[学科分类] 工业工程学

[关键词] AXDND1;manchette;nuclear shaping;spermiogenesis;sterility