Retinoblastoma protein plays multiple essential roles in the terminal differentiation of Sertoli cells.
Animals, Apoptosis, Cell-Differentiation, G1-Phase, Genes-p53, Mice-Knockout, Models-Biological, Retinoblastoma-Protein, S-Phase, Sertoli-Cells, Testis, Tumor-Suppressor-Protein-p53
Mol Endocrinol 2009 Nov; 23(11):1900-13.
Retinoblastoma protein (RB) plays crucial roles in cell cycle control and cellular differentiation. Specifically, RB impairs the G(1) to S phase transition by acting as a repressor of the E2F family of transcriptional activators while also contributing towards terminal differentiation by modulating the activity of tissue-specific transcription factors. To examine the role of RB in Sertoli cells, the androgen-dependent somatic support cell of the testis, we created a Sertoli cell-specific conditional knockout of Rb. Initially, loss of RB has no gross effect on Sertoli cell function because the mice are fertile with normal testis weights at 6 wk of age. However, by 10-14 wk of age, mutant mice demonstrate severe Sertoli cell dysfunction and infertility. We show that mutant mature Sertoli cells continue cycling with defective regulation of multiple E2F1- and androgen-regulated genes and concurrent activation of apoptotic and p53-regulated genes. The most striking defects in mature Sertoli cell function are increased permeability of the blood-testis barrier, impaired tissue remodeling, and defective germ cell-Sertoli cell interactions. Our results demonstrate that RB is essential for proper terminal differentiation of Sertoli cells.
Nalam, R L.; Andreu, Vieyra C.; Braun, R E.; Akiyama, H; and Matzuk, M M., "Retinoblastoma protein plays multiple essential roles in the terminal differentiation of Sertoli cells." (2009). Faculty Research 2000 - 2009. 2084.