Testis-specific Protein Kinases TSSK1 and TSSK2 in Mouse Spermiogenesis

Abstract

In this thesis, author systematically studied two testis-specific protein kinases TSSK1 and TSSK2 in mouse spermiogenesis. By building a double knockout mouse model with the absence of Tssk1 and Tssk2 genes, it was demonstrated that TSSK1 and TSSK2 are essential for male fertility in mouse, and the homozygous male mutants missing these two kinases are infertile. In addition, TSSK1 and TSSK2, together with their common substrate, TSKS, are involved into the chromatoid body (CB) transformation during spermatid elongation. By co-IP and following proteomics analyses, it was shown that TSSK1, TSSK2, and TSKS can form a stable protein complex, named as TSSK1/2-TSKS complex, which is involved into RNA regulation, protein phorsphorylation and cytoskeleton regulation. Further evolutionary studies displayed that TSSK1 and TSSK2 gained diverse functions during evolution, although Tssk1 and Tssk2 are a pair of duplicated genes, and TSSK1 and TSSK2 are highly homologous. Because of the testis-specificty, late expression, and the indispensability to male fertility, TSSK1 and TSSK2 are potential drug targets for non-hormonal contraceptives