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Atm ‐null mice exhibit enhanced radiation‐induced birth defects and a hybrid form of embryonic cell death indicating a teratological suppressor function for ATM
Author(s) -
Laposa Rebecca R.,
Henderson Jeffrey T.,
Xu Elaine,
Wells Peter G.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0903fje
Subject(s) - programmed cell death , ataxia telangiectasia , apoptosis , biology , embryo , embryonic stem cell , dna damage , microbiology and biotechnology , andrology , cancer research , genetics , gene , dna , medicine
ATM (ataxia‐telangiectasia mutated) is a genotoxic stress transducer. In this first report of Atm ‐ dependent birth defects, Atm ‐null embryos were uniquely susceptible to low‐dose (0.5 Gy) radiation, exhibiting severe runting, tail anomalies, and lethality, independent of cell cycle arrest or insulin‐like growth factor 1. This treatment enhanced levels of p53 protein and central nervous system (CNS) apoptosis in wild‐type mice, but not Atm ‐null mutants, at 6 h postirradiation. At 48 h, however, this pattern was reversed, with Atm ‐null mice exhibiting high levels of a hybrid form of programmed cell death within the CNS. Even heterozygous Atm ‐ deficient embryos were radiosensitive to a higher radiation dose of 2 Gy. These results show that Atm is a novel teratologic suppressor gene protecting embryos from pathological cell death and teratogenesis initiated by even mild DNA damage.