title: Accentuated apoptosis in normally developing p53 knockout mouse embryos following genotoxic stress.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Assaf Harofe, Medical Center, Tel Aviv University, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Frenkel
authors.forename: D
authors.initials: D
authors.lastname: Sherman
authors.forename: A
authors.initials: A
authors.lastname: Fein
authors.forename: D
authors.initials: D
authors.lastname: Schwartz
authors.forename: N
authors.initials: N
authors.lastname: Almog
authors.forename: A
authors.initials: A
authors.lastname: Kapon
authors.forename: N
authors.initials: N
authors.lastname: Goldfinger
authors.forename: V
authors.initials: V
authors.lastname: Rotter
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000528:radiation effects; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005260:Female; D005720:Gamma Rays; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009436:Neural Tube Defects / Q000235:genetics; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53