Taccioli GE, Amatucci AG, Beamish HJ, Gell D, Xiang XH, Arzayus MIT, Priestley A, Jackson SP, Rothstein AM, Jeggo PA and Herrera VLM. (1998) Targeted disruption of the catalytic subunit of the DNA PK gene in mice confers severe combined immunodeficiency and radiosensitivity. Immunity 9, 355-366.

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.