File(s) not publicly available
Targeted disruption of the catalytic subunit of the DNA-PK gene in mice confers severe combined immunodeficiency and radiosensitivity
journal contributionposted on 2023-05-17, 02:59 authored by Taccioli, GE, Amatucci, AG, Beamish, HJ, David GellDavid Gell, Xiang, XH, Torres Arzayus, MI, Priestley, A, Jackson, SP, Marshak Rothstein, A, Jeggo, PA, Herrera, VL
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.
Department/SchoolMenzies Institute for Medical Research
Place of publication1100 Massachusetts Ave, Cambridge, USA, Ma, 02138