| First Author | Nalam RL | Year | 2009 |
| Journal | Mol Endocrinol | Volume | 23 |
| Issue | 11 | Pages | 1900-13 |
| PubMed ID | 19819985 | Mgi Jnum | J:154066 |
| Mgi Id | MGI:4367160 | Doi | 10.1210/me.2009-0184 |
| Citation | Nalam RL, et al. (2009) Retinoblastoma protein plays multiple essential roles in the terminal differentiation of Sertoli cells. Mol Endocrinol 23(11):1900-13 |
| abstractText | 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. |
