Targeted disruption of the catalytic subunit of the DNA-PK gene in mice confers severe combined immunodeficiency and radiosensitivity.
- 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.
- Authors:
- GE Taccioli, AG Amatucci, HJ Beamish, D Gell, XH Xiang, MI Torres Arzayus, A Priestley, SP Jackson, A Marshak Rothstein, PA Jeggo, VL Herrera
- Journal:
- Immunity
- Citation info:
- 9(3):355-366
- Publication date:
- 1st Jan 1998
- Full text
- DOI