Sox30 is a member of the Sox (Sry-related HMG box) gene family, members of which encode transcription factors that are highly conserved and are important for regulating gene expression in a range of developmental processes. We recently reported that SOX30 is critically required for male fertility1: when Sox30 is deleted, either ubiquitously or germ cell-specifically, spermatogenesis arrests at the round spermatid stage. The Sox30-null phenotype resembles that of CREM mutant mice, suggesting that SOX30 and CREM may interact, structurally or functionally, to regulate the spermiogenesis phase of spermatogenesis.
The infertility phenotype of the pan-CREM mutants was reported over two decades ago2,3, however further research regarding the role of Crem in spermatogenesis is complicated by its large number of isoforms and complexity of their pattern of expression and function. Using precise genome editing techniques, we are attempting to address this complexity by ablating specific Crem isoforms. Further, to determine which, if any, CREM isoforms physically interact with SOX30 as we predict, we have used genome editing to generate a novel SOX30-V5-tagged mouse line. This approach will allow us to employ immunoprecipitation as well as ChIP to identify SOX30-interacting proteins, and direct transcriptional targets.
Our fundamental developmental biology studies, uncovering new interactions and transcriptional targets of transcription factors critical for fertility, will inform our understanding of non-obstructive azoospermia (NOA), a form of male infertility characterized by the complete absence of sperm: this condition cannot be overcome using conventional assisted reproduction techniques. Our findings may also contribute to ongoing international efforts to develop a safe effective approach to male contraception.