Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Institute for Biology, University of Lübeck, Lübeck, Germany.
PLoS One. 2024 Oct 18;19(10):e0304189. doi: 10.1371/journal.pone.0304189. eCollection 2024.
The nuclear transport of proteins is mediated by karyopherins and has been implicated to be crucial for germ cell and embryonic development. Deletion of distinct members of the karyopherin alpha family has been shown to cause male and female infertility in mice. Using a genetrap approach, we established mice deficient for KPNA2 (KPNA2 KO) and investigated the role of this protein in male germ cell development and fertility. Breeding of male KPNA2 KO mice leads to healthy offsprings in all cases albeit the absence of KPNA2 resulted in a reduction in sperm number by 60%. Analyses of the KPNA2 expression in wild-type mice revealed a strong KPNA2 presence in meiotic germ cells of all stages while a rapid decline is found in round spermatids. The high KPNA2 expression throughout all meiotic stages of sperm development suggests a possible function of KPNA2 during this phase, hence in its absence the spermatogenesis is not completely blocked. In KPNA2 KO mice, a higher portion of sperms presented with morphological abnormalities in the head and neck region, but a severe spermiogenesis defect was not found. Thus, we conclude that the function of KPNA2 in round spermatids is dispensable, as our mice do not show any signs of infertility. Our data provide evidence that KPNA2 is not crucial for male germ cell development and fertility.
蛋白质的核转运是由核孔蛋白介导的，对于生殖细胞和胚胎发育至关重要。核孔蛋白α家族的不同成员的缺失已被证明会导致小鼠的雄性和雌性不育。我们使用基因捕获方法建立了 KPNA2 缺陷（KPNA2 KO）的小鼠，并研究了该蛋白在雄性生殖细胞发育和生育力中的作用。尽管 KPNA2 的缺失导致精子数量减少了 60%，但 KPNA2 KO 雄性小鼠的繁殖导致所有情况下都有健康的后代。对野生型小鼠中 KPNA2 的表达分析表明，KPNA2 在所有阶段的减数分裂生殖细胞中都有很强的存在，而在圆形精子中则迅速下降。KPNA2 在精子发生的所有减数分裂阶段的高表达表明 KPNA2 在该阶段可能具有功能，因此在其缺失的情况下，精子发生并没有完全受阻。在 KPNA2 KO 小鼠中，更多的精子头部和颈部区域呈现形态异常，但没有发现严重的精子发生缺陷。因此，我们得出结论，KPNA2 在圆形精子中的功能是可有可无的，因为我们的小鼠没有表现出任何不育迹象。我们的数据提供了证据表明，KPNA2 对雄性生殖细胞发育和生育力不是至关重要的。
