Retinoblastoma protein represses E2F3 to maintain Sertoli cell quiescence in mouse testis

Abstract

<p>Maintenance of the differentiated state and cell cycle exit in adult Sertoli cells depends on tumor suppressor retinoblastoma protein (RB, also known as RB1). We have previously shown that RB interacts with transcription factor E2F3 in the mouse testis. Here, we investigated how <em>E2f3</em> contributes to adult Sertoli cell proliferation in a mouse model of Sertoli cell-specific knockout of <em>Rb</em> by crossing these mice with an <em>E2f3</em> knockout mouse line. In the presence of intact RB, <em>E2f3</em> was redundant in Sertoli cells. However, in the absence of RB, <em>E2f3</em> is a key driver for cell cycle re-entry and loss of function in adult Sertoli cells. Knockout of <em>E2f3</em> in Sertoli cells rescued the breakdown of Sertoli cell function associated with <em>Rb</em> loss, prevented proliferation of adult Sertoli cells and restored fertility of the mice. In summary, our results show that RB-mediated repression of E2F3 is critical for the maintenance of cell cycle exit and terminal differentiation in adult mouse Sertoli cells.</p>