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

Oncogene. 1999 May 6;18(18):2901-7. doi: 10.1038/sj.onc.1202518.


In order to identify the alternative pathways which may substitute for the p53 function during embryogenesis, we have focused our studies on p53 -/- normally developing mouse embryos that survived a genotoxic stress. We assumed that under these conditions p53-independent pathways, which physiologically control genomic stability, are enhanced. We found that while p53 +/+ mouse embryos elicited, as expected, a p53-dependent apoptosis, p53-/- normally developing mice exhibited an accentuated p53-independent apoptotic response. The p53-dependent apoptosis detected in p53+/+ embryos, was an immediate reaction mostly detected in the brain, whereas the p53-independent apoptosis was a delayed reaction with a prominent pattern observed in epithelial cells of most organs in the p53-deficient mice only. These results suggest that 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Embryo, Mammalian / cytology*
  • Embryo, Mammalian / radiation effects
  • Embryonic and Fetal Development / genetics*
  • Female
  • Gamma Rays
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Neural Tube Defects / genetics
  • Stress, Physiological
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism


  • Tumor Suppressor Protein p53