PDF(Pubmed)
Abstract：
By analyzing a mouse Interspecific Recombinant Congenic Strain (IRCS), we previously identified a quantitative trait locus (QTL), called Mafq1 on mouse chromosome 1, that is associated with male hypofertility and ultrastructural sperm abnormalities. Within this locus, we identified a new candidate gene that could be implicated in a reproductive phenotype: Tex44 (Testis-expressed protein 44). We thus performed a CRISPR/Cas9-mediated complete deletion of this gene in mice in order to study its function. Tex44-KO males were severely hypofertile in vivo and in vitro due to a drastic reduction of sperm motility which itself resulted from important morphological sperm abnormalities. Namely, Tex44-KO sperm showed a disorganized junction between the midpiece and the principal piece of the flagellum, leading to a 180° flagellar bending in this region. In addition, the loss of some axonemal microtubule doublets and outer dense fibers in the flagellum\'s principal piece has been observed. Our results suggest that, in mice, TEX44 is implicated in the correct set-up of the sperm flagellum during spermiogenesis and its absence leads to flagellar abnormalities and consequently to severe male hypofertility.
摘要：
通过分析小鼠种间重组同源菌株（IRCS），我们以前确定了一个数量性状基因座(QTL)，在小鼠1号染色体上称为Mafq1，与男性低生育力和超微结构精子异常有关。在这个轨迹中，我们确定了一个可能与生殖表型有关的新候选基因:Tex44(睾丸表达蛋白44).因此，我们在小鼠中进行了CRISPR/Cas9介导的该基因的完全缺失，以研究其功能。Tex44-KO雄性在体内和体外的生育能力严重低下，这是由于重要的精子形态异常导致的精子活力急剧下降。即,Tex44-KO精子在中段和鞭毛的主要部分之间显示出杂乱无章的连接，导致该区域鞭毛弯曲180°。此外,已经观察到鞭毛主片中一些轴突微管双峰和外部致密纤维的损失。我们的研究结果表明,在老鼠身上，TEX44与精子发生过程中精子鞭毛的正确设置有关，其缺失会导致鞭毛异常，从而导致严重的男性生育能力低下。
