UNSCHEDULED DNA-REPLICATION PRECEDES APOPTOSIS OF PHOTORECEPTORS EXPRESSING SV40 T-ANTIGEN

Expression of simian virus 40 T antigen (Tag) in the rod photoreceptor s of transgenic mice leads to cell death that is completed by the end of the third week of postnatal development. To understand the mechanis tic link between Tag expression and the death of the expressing photor eceptors, cell cycle activity was followed in a transgenic mouse famil y that expresses Tag directed by the mouse opsin promoter. Tag-express ing photoreceptors also expressed rhodopsin suggesting that these cell s were differentiated. The presence of Tag in the photoreceptors induc ed the expression of both proliferating cell nuclear antigen (PCNA) an d thymidine kinase (TK). The abnormally high levels of PCNA and TK con tinued until the complete disappearance of the cells expressing Tag. P hotoreceptor cell death was also associated with continued DNA synthes is that ceased shortly after postnatal day 16. The specific loss of th e rod photoreceptors that re-entered the cell cycle accounted entirely for the loss of photoreceptors from the outer nuclear layer. The anti proliferative nature of the mature retina is directly involved in the apoptotic death of photoreceptors expressing Tag. (C) 1997 Academic Pr ess Limited.