title: Atm and c-Abl cooperate in the response to genotoxic stress during nervous system development.
abstract: The c-Abl proto-oncogene is a target of the ATM kinase after DNA double strand breaks, although the physiological significance of these signaling events is not clear. Therefore, to delineate the roles of c-Abl and Atm during mouse development we generated mice with combinations of c-Abl and Atm mutant alleles. We found that dual inactivation of Atm and c-Abl usually resulted in midgestational lethality. However, mice with three mutant alleles, c-Abl(-/-)Atm(+/-) or c-Abl(+/-)Atm(-/-), were viable but predisposed to neuro-developmental abnormalities after genotoxic insult. Thus, these genetic data link Atm and c-Abl signaling and underscore a significant interrelationship between the two during neural development.
mesh_terms: D000483:Alleles; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004249:DNA Damage / Q000502:physiology*; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000528:radiation effects; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000528:radiation effects; D005720:Gamma Rays; D016313:Genes, abl / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D009420:Nervous System / Q000196:embryology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D015996:Survival Rate; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases