Accentuated apoptosis in normally developing p53 knockout mouse embryos following genotoxic stress

In order to identify the alternative pathways which may substitute for the p53 function during embryogenesis, we have focused our studies on p53-/- no rmally developing mouse embryos that survived a genotoxic stress. We assume d that under these conditions p53-independent pathways, which physiological ly control genomic stability, are enhanced. We found that while p53+/+ mous e embryos elicited, as expected, a p53-dependent apoptosis, p53-/- normally developing mice exhibited an accentuated p53-independent apoptotic respons e. The p53-dependent apoptosis detected in p53+/+ embryos, was an immediate reaction mostly detected in the brain, whereas the p53-independent apoptos is was a delayed reaction with a prominent pattern observed in epithelial c ells of most organs in the p53-deficient mice only. These results suggest t hat in the absence of p53-dependent apoptosis, which is a fast response to damaged DNA, p53-independent apoptotic pathways, with slower kinetics, are turned on to secure genome stability.