TARGETED DISRUPTION OF THE CATALYTIC SUBUNIT OF THE DNA-PK GENE IN MICE CONFERS SEVERE COMBINED IMMUNODEFICIENCY AND RADIOSENSITIVITY

Citation
Ge. Taccioli et al., TARGETED DISRUPTION OF THE CATALYTIC SUBUNIT OF THE DNA-PK GENE IN MICE CONFERS SEVERE COMBINED IMMUNODEFICIENCY AND RADIOSENSITIVITY, Immunity (Cambridge, Mass.), 9(3), 1998, pp. 355-366
Citations number
74
Categorie Soggetti
Immunology
Journal title
ISSN journal
10747613
Volume
9
Issue
3
Year of publication
1998
Pages
355 - 366
Database
ISI
SICI code
1074-7613(1998)9:3<355:TDOTCS>2.0.ZU;2-H
Abstract
The DNA-dependent protein kinase is a mammalian protein complex compos ed of Ku70, Ku80, and DNA-PKcs subunits that has been implicated in DN A double-strand break repair and V(D)J recombination. Here, by gene ta rgeting, we have constructed a mouse with a disruption in the kinase d omain 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 DN A-PKcs defective mice closely resemble Scid mice, they differ by havin g elevated numbers of CD4(+)CD8(+) thymocytes. This suggests that the Scid mice may not represent a null phenotype and may retain some resid ual DNA-PKcs function.