Retinoblastoma tumor suppressor protein (RB) controls the G1-S transition in the cell cycle and has been linked to DNA damage responses, DNA repair and DNA replication, apoptosis and differentiation (Classon & Harlow 2002). In the testis RB expression is temporally and spatially controlled (Yan, W. et al. 2001) and some testicular germ cell tumors lack normal RB expression (Bartkova, J. et al. 2003). RB is expressed by spermatogonia and Sertoli cells (SC) in the mouse testis. The aim of our present study is to dissect the role of RB in SC proliferation, differentiation and function in the control of spermatogenesis. For this purpose we created a Sertoli cell specific Rb knockout mouse model (SC- RbKO) using the cre-lox technology. SC-RbKO mice have a progressive testicular phenotype which leads to infertility. Adult SC-RbKO mice have markedly smaller testes than the control animals as a result of disruption of spermatogenesis with disintegration of SC-germ cell contacts and apoptosis of germ cells. SC proliferation in the immature testis is similar in the knockout and wild-type testes. However at the age of 1 month SCs resume proliferation in the SC-RbKO suggesting a cell cycle deregulation. Moreover, adult SC-RbKO testes show evidence of SC immaturity and disorganization of inter-Sertoli cell tight junctions. By the age of 3 months not only germ cells but also SCs undergo apoptosis. Taken together, our findings show that retinoblastoma protein is essential for Sertoli cell function and hence an important regulator of spermatogenesis.

References: 

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