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
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.