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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alleles
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Animals
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Ataxia Telangiectasia Mutated Proteins
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Cell Cycle Proteins
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DNA Damage / physiology*
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DNA-Binding Proteins
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Embryo, Mammalian / abnormalities
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Embryo, Mammalian / radiation effects
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Embryonic and Fetal Development* / genetics
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Embryonic and Fetal Development* / radiation effects
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Gamma Rays
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Genes, abl / genetics
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Genes, abl / physiology*
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Immunohistochemistry
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Mice
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Mice, Knockout / embryology
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Mice, Knockout / growth & development
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Mice, Knockout / metabolism
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Nervous System* / embryology
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Nervous System* / metabolism
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / physiology*
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Survival Rate
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Tumor Suppressor Proteins
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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Tumor Suppressor Proteins
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Ataxia Telangiectasia Mutated Proteins
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Atm protein, mouse
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Protein Serine-Threonine Kinases