Requirement for Atm in ionizing radiation-induced cell death in the developing central nervous system.
Ataxia telangiectasia (AT) is characterized by progressive neurodegeneration that results from mutation of the ATM gene. However, neither the normal function of ATM in the nervous system nor the biological basis of the degeneration in AT is known. Resistance to apoptosis in the developing central nervous system (CNS) of Atm-/- mice was observed after ionizing radiation. This lack of death occurred in diverse regions of the CNS, including the cerebellum, which is markedly affected in AT. In wild-type, but not Atm-/- mice, up-regulation of p53 coincided with cell death, suggesting that Atm-dependent apoptosis in the CNS is mediated by p53. Further, p53 null mice showed a similar lack of radiation-induced cell death in the developing nervous system. Atm may function at a developmental survival checkpoint that serves to eliminate neurons with excessive DNA damage.
Herzog
K H
KH
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38101, USA.
Chong
M J
MJ
Kapsetaki
M
M
Morgan
J I
JI
McKinnon
P J
PJ
D000818:Animals; D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D001921:Brain / Q000166:cytology* / Q000528:radiation effects*; D018797:Cell Cycle Proteins; D002531:Cerebellum / Q000166:cytology / Q000528:radiation effects; D004268:DNA-Binding Proteins; D016158:Genes, p53; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000528:radiation effects; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011839:Radiation, Ionizing; D012160:Retina / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases