Targeted expression of SV40 large tumour antigen (TAg) induces a transientenhancement of spermatocyte proliferation and apoptosis

In an attempt to determine the susceptibility of spermatocytes to malignant transformation by simian virus 40 (SV40) large tumour antigen (TAg), trans genic mice harbouring a chimeric gene composed of the SV40 TAg gene fused t o the 1.4 kb promoter sequence of the human phosphoglycerate kinase 2 (PGK2 ) gene were generated. Northern blot analysis on RNA from different tissues indicated a specific transcription of TAg in the testis of PGK2-TAg transg enic mice. Reverse transcription-polymerase chain reaction and Western blot analysis on testes at different stages of development revealed that transc ription and translation of the TAg gene starts in 12-day-old testis, which coincides with the appearance of pre-leptotene spermatocytes. Germ cells of transgenic mice showed no tendency toward transformation, but in testes of both 18- and 25-day-old transgenic mice, a significantly enhanced number o f spermatocytes was found. In contrast, in 42-day-old transgenic mice no di fferences in the number of spermatocytes and spermatids were observed. The number of Sertoli cells was determined to be equal in transgenic and wild t ype mice. In-situ end labelling of fragmented DNA revealed a higher rate of apoptosis in testes of 18-day-old transgenic mice as compared with wild ty pe mice. These results indicate that germ cell homeostasis in transgenic mi ce is maintained by an apoptotic mechanism.