Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Exp Anim. 2020 Nov 12;69(4):374-381. doi: 10.1538/expanim.20-0064. Epub 2020 Jun 18.
Infertility is a global health issue that affects 1 in 6 couples, with male factors contributing to 50% of cases. The flagellar axoneme is a motility apparatus of spermatozoa, and disruption of its structure or function could lead to male infertility. The axoneme consists of a "9+2" structure that contains a central pair of two singlet microtubules surrounded by nine doublet microtubules, in addition to several macromolecular complexes such as dynein arms, radial spokes, and nexin-dynein regulatory complexes. Molecular components of the flagellar axoneme are evolutionally conserved from unicellular flagellates to mammals, including mice. Although knockout (KO) mice have been generated to understand their function in the formation and motility regulation of sperm flagella, the majority of KO mice die before sexual maturation due to impaired ciliary motility, which makes it challenging to analyze mature spermatozoa. In this review, we introduce methods that have been used to overcome premature lethality, focusing on KO mouse lines of central pair components.
不育症是一个全球性的健康问题，影响了 1/6 的夫妇，其中男性因素导致了 50%的病例。鞭毛轴丝是精子的运动器官，其结构或功能的破坏可能导致男性不育。轴丝由“9+2”结构组成，包含一对中央的两条单体微管，周围环绕着九条双体微管，此外还有一些大分子复合物，如动力蛋白臂、辐条和连接蛋白-动力蛋白调节复合物。鞭毛轴丝的分子成分从单细胞鞭毛虫到哺乳动物（包括小鼠）都是进化保守的。尽管已经产生了敲除（KO）小鼠来了解它们在精子鞭毛形成和运动调节中的作用，但由于纤毛运动受损，大多数 KO 小鼠在性成熟前死亡，这使得分析成熟的精子变得具有挑战性。在这篇综述中，我们介绍了克服过早致死性的方法，重点介绍了中央对组件的 KO 小鼠系。
