title: Retinoblastoma protein plays multiple essential roles in the terminal differentiation of Sertoli cells.
abstract: 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.
authors.affiliation: Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: Roopa L
authors.initials: RL
authors.lastname: Nalam
authors.forename: Claudia
authors.initials: C
authors.lastname: Andreu-Vieyra
authors.forename: Robert E
authors.initials: RE
authors.lastname: Braun
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Martin M
authors.initials: MM
authors.lastname: Matzuk
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D016193:G1 Phase; D016158:Genes, p53; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016196:S Phase; D012708:Sertoli Cells / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000728:Androgens; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53