Requirement for Atm in Ionizing Radiation-Induced Cell Death in the Developing Central Nervous System

Publisher Website
Google Scholar
Abstract
Ataxia telangiectasia (AT) is characterized by progressive neurodegeneration that results from mutation of the ATMgene. 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) ofAtm−/− 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.