Targeted Disruption of the Catalytic Subunit of the DNA-PK Gene in Mice Confers Severe Combined Immunodeficiency and Radiosensitivity

• Published in: Immunity (Cambridge, Mass.) Mass.), 1998-09, Vol.9 (3), p.355-366
• Main Authors: Taccioli, Guillermo E, Amatucci, Aldo G, Beamish, Heather J, Gell, David, Xiang, Xie H, Arzayus, Maria I.Torres, Priestley, Ann, Jackson, Stephen P, Rothstein, Ann Marshak, Jeggo, Penny A, Herrera, Victoria L.M
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - cytology; Catalysis; Cell Differentiation - genetics; Cells, Cultured; DNA-Activated Protein Kinase; DNA-Binding Proteins; Embryo, Mammalian; Fibroblasts - radiation effects; Gene Targeting; Genes, T-Cell Receptor - genetics; Immunoglobulins - genetics; Mice; Mice, Inbred C57BL; Mice, Transgenic; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - physiology; Radiation Tolerance - genetics; Recombination, Genetic - genetics; Severe Combined Immunodeficiency - genetics; T-Lymphocytes - cytology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)80618-4

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.