Testicular wild-type p53 expression in transgenic mice induces spermiogenesis alterations ranging from differentiation defects to apoptosis

While p53 is dispensable for development, an excess of p53 has dramatic con sequences on the embryogenesis and on the cell differentiation. In an attem pt to analyse in vivo the effects of p53 activity, we have generated transg enic mice expressing the wild-type p53 under the control of the metallothio nein I promoter. In the three transgenic lines established, exogenous p53 i s expressed constitutively in the postmeiotic cells of transgenic males and two lines are subfertile, Transgenic males expressing the upper level of p 53 produce few spermatozoa since the majority of developing spermatids unde rgo apoptosis, In the subfertile males exhibiting an intermediate amount of p53, teratozoospermia is obvious suggesting an altered terminal differenti ation of postmeiotic cells. In contrast lower level of p53 does not lead th e third line to sterility. These results suggest that the activity of p53 i s dependent irt vivo on the amount of p53 present within cells, as it has b een already demonstrated in vitro.