Srsf1-flox Mouse

Srsf1, the founding member of the SR protein family, is a splicing factor crucial for pre-mRNA splicing and regulation of various alternative splicing events [2]. It is involved in numerous biological processes and associated pathways. Dysregulation of Srsf1 expression contributes to cancer and other pathologies [2]. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.

Male germ cell-specific deletion of Srsf1 in mice led to complete infertility by affecting spermatogenesis. Srsf1 affected the alternative splicing of Stra8 directly and that of Dazl, Dmc1, Mre11a, Syce2 and Rif1 indirectly [3]. In the context of pancreatic diseases, increased Srsf1 in mice is sufficient to induce pancreatitis and accelerate KRASG12D-mediated pancreatic ductal adenocarcinoma (PDAC). Srsf1 activates MAPK signaling, in part by upregulating interleukin 1 receptor type 1 (IL1R1) through alternative-splicing-regulated mRNA stability [1].

In conclusion, Srsf1 is essential for spermatogenesis and male fertility through its role in alternative splicing. In pancreas-related diseases, it plays a significant role in the etiology of pancreatitis and PDAC. The study of Srsf1 using KO/CKO mouse models provides insights into its functions in these specific biological processes and disease conditions.