DNA-DEPENDENT KINASE (P350) AS A CANDIDATE GENE FOR THE MURINE SCID DEFECT

Severe combined immunodeficient (SCID) mice are deficient in a recombi nation process utilized in both DNA double-strand break repair and in V(D)J recombination. The phenotype of these mice involves both cellula r hypersensitivity to ionizing radiation and a lack of B and T cell im munity. The catalytic subunit of DNA-dependent protein kinase, p350, w as identified as a strong candidate for the murine gene SCID. Both p35 0 and a gene complementing the SCID defect colocalize to human chromos ome 8q11. Chromosomal fragments expressing p350 complement the SCID ph enotype, and p350 protein levels are greatly reduced in cells derived from SCID mice compared to cells from wild-type mice.