精子发生是复杂的细胞分裂分化过程，阶段特异性表达的蛋白质在其中发挥关键的调控作用。因为很多新合成的前体蛋白需经酶切激活方能发挥功能，所以蛋白酶的作用受到关注。TMPRSSs是近年来发现的一组膜锚定蛋白酶，部分成员在不同生理过程中的作用及其与相应疾病的关联已得到证实。我们前期发现构建的人睾丸蛋白质表达谱中有TMPRSS成员——TMPRSS12。初步研究显示TMPRSS12在睾丸特异表达，主要定位于精子细胞，但成熟精子无表达；缺失TMPRSS12的雄性小鼠不育，精子活力显著下降；提示TMPRSS12可能在精子细胞变形过程中发挥功能，影响精子活力。本课题拟通过TMPRSS12定位研究和基因敲除小鼠表型分析，揭示TMPRSS12影响精子活力的具体环节，同时筛选TMPRSS12在发挥功能时的底物蛋白及其下游分子网络，全面阐明TMPRSS12在精子发生中的作用和机制，并验证该基因在不育人群的关联性。

Spermatogenesis is a complex process of cell division and differentiation, which is regulated by stage-specific expression of a series proteins. Because a lot of newly synthesized precursor proteins need cleavage for transforming into active protein, the role of protease attracts highly concerned. In recent years a group of membrane anchored proteases, TMPRSSs, has emerged. Studies on some members of this protease family have indicated they participated in regulating different physiological processes, and disease association has been confirmed. By constructing the protein expression profile of human testis, we found there is a function unknown TMPRSS member, TMPRSS12, in the testis. Our preliminary study demonstrate that TMPRSS12 is specifically expressed in testis, and predominantly expressed in spermatid, but not expressed in mature sperm; in mouse model, TMPRSS12 deficiency cause sperm motility significantly decreased and male infertility. These results suggest that TMPRSS12 may play a role during spermiogenesis. In this project, through in-depth analysis of TMPRSS12 knockout mice, we will reveal the specific aspects of TMPRSS12's effect on sperm motility, and further find its specific substrate protein and molecular regulation network. Our stuy could provide an overall view of TMPRSS12 in regulation of spermiogenesis.