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Targeted disruption of the catalytic subunit of the DNA-PK gene in mice confers severe combined immunodeficiency and radiosensitivity

Citation

Taccioli, GE and Amatucci, AG and Beamish, HJ and Gell, D and Xiang, XH and Torres Arzayus, MI and Priestley, A and Jackson, SP and Marshak Rothstein, A and Jeggo, PA and Herrera, VL, Targeted disruption of the catalytic subunit of the DNA-PK gene in mice confers severe combined immunodeficiency and radiosensitivity , Immunity, 9, (3) pp. 355-366. ISSN 1074-7613 (1998) [Refereed Article]

DOI: doi:10.1016/S1074-7613(00)80618-4

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.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Enzymes
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Gell, D (Dr David Gell)
ID Code:64589
Year Published:1998
Web of Science® Times Cited:228
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-08-12
Last Modified:2011-08-10
Downloads:0

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