The product of the ATM gene is a 370-kDa nuclear phosphoprotein

Neuronal degeneration, gonadal abnormalities, and immune deficiency are some of the major manifestations of the hereditary disease ataxia telangiectasia, which is caused by mutations in a single gene, designated ATM. Here we show that the product of the ATM gene is a 370-kDa nuclear phosphoprotein. Because ATM knockout mice recapitulate the clinical symptoms of the human disease, we have examined ATM gene expression in mice. In mouse embryos at gestation day 13.5, ATM mRNA is expressed ubiquitously, with high levels detected in the nervous system and lung. Elevated ATM mRNA levels were also found in the thymus of mouse embryos at gestation day 18.5, a time when V(D)J recombination is occurring. In adult mice, ATM protein was detected in all tissues examined and was present at elevated levels in the testis, spleen, and thymus. The ATM expression pattern and the nuclear localization of the ATM protein are consistent with the proposed function of ATM in the activation of cell cycle checkpoints, DNA repair, and genetic recombination.