Abstract
The DNA-dependent protein kinase is a mammalian protein complex composed of Ku70, Ku80, and DNA-PKcs subunits that has been implicated in DNA double-strand break repair and V(D)J recombination. Here, by gene targeting, we have constructed a mouse with a disruption in the kinase domain of DNA-PKcs, generating an animal model completely devoid of DNA-PK activity. Our results demonstrate that DNA-PK activity is required for coding but not for signal join formation in mice. Although our DNA-PKcs defective mice closely resemble Scid mice, they differ by having elevated numbers of CD4+CD8+ thymocytes. This suggests that the Scid mice may not represent a null phenotype and may retain some residual DNA-PKcs function.
Publication types
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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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Animals
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B-Lymphocytes / cytology
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Catalysis
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Cell Differentiation / genetics
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Cells, Cultured
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DNA-Activated Protein Kinase
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DNA-Binding Proteins*
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Embryo, Mammalian
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Fibroblasts / radiation effects
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Gene Targeting*
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Genes, T-Cell Receptor / genetics
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Immunoglobulins / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Protein Serine-Threonine Kinases / chemistry*
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / physiology
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Protein Structure, Tertiary
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Radiation Tolerance / genetics*
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Recombination, Genetic / genetics
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Severe Combined Immunodeficiency / genetics*
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T-Lymphocytes / cytology
Substances
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DNA-Binding Proteins
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Immunoglobulins
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DNA-Activated Protein Kinase
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Protein Serine-Threonine Kinases