Cloning and chromosomal mapping of the mouse DNA-dependent protein kinase gene

Severe combined immune deficiency (scid) mice are assumed to have two types of abnormalities: one is high radiosensitivity and the other is abnormal recombination in immunoglobulin and T-cell receptor genes. The human chromosome 8 q1.1 region has an ability to complement the scid aberration. Moreover, the localization of the subunit DNA-dependent protein kinase [DNA-PKcs] participating in DNA double-strand break repair in the same locus was clarified. In acid mouse cells, the number of DNA-PKcs products and extent of DNA-PK activity remarkably decrease. These observations gave rise to the assumption that DNA-PKcs is the scid factor itself. In order to determine whether the DNA-PKcs gene is the scid gene, we isolated the mouse DNA-PKcs gene and investigated its chromosomal locus by fluorescence in situ hybridization (FISH). Consequently, it became clear that the mouse DNA PKcs gene existed in the centromeric region of mouse chromosome 16, determined by cross-genetic study, as a scid locus. This finding strongly suggests that mouse DNA-PKcs is the scid gene.