absence of inhibin alpha and retinoblastoma protein leads to early sertoli cell dysfunction缺乏抑制素α和视网膜母细胞瘤蛋白导致早期滋养细胞功能障碍.pdfVIP

Absence of Inhibin Alpha and Retinoblastoma Protein Leads to Early Sertoli Cell Dysfunction Roopa L. Nalam1,2, Claudia Andreu-Vieyra1¤, Martin M. Matzuk1,2,3* 1 Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America, 2 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America, 3 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America Abstract Sertoli cells, the support cells of mammalian spermatogenesis, are regulated by a number of nuclear factors and express retinoblastoma (RB) tumor suppressor protein. We hypothesized that RB is an important mediator of Sertoli cell tumorigenesis in inhibin a knockout (Inha KO) mice. In our previous mouse studies, we found that conditional knockout (cKO) of Rb in Sertoli cells caused progressive Sertoli cell dysfunction. Initially, loss of RB had no gross effect on Sertoli cell function as the mice were fertile with normal testis weights at 6 weeks of age, but by 10–14 weeks of age, mutant mice demonstrated severe Sertoli cell dysfunction and infertility. Although double knockout (dKO) of Rb and Inha did not result in exacerbation of the tumorigenic phenotype of Inha-null mice, we found that the dKO mice demonstrate an acceleration of Sertoli cell dysfunction compared to Rb cKO mice. Specifically, in contrast to Rb cKO mice, Inha/Rb dKO mice showed signs of Sertoli cell dysfunction as early as 4 weeks of age. These results demonstrate that RB is not essential for Sertoli cell tumorigenesis in Inha KO mice but that loss of Inha accelerates the infertility phenotype of Rb cKO mice. Citation: Nalam RL, Andreu-Vieyra C, Matzuk MM (2010) Absence of Inhibin Alpha and Retinoblastoma Protein Leads to Early Sertoli Cell Dys