GROWTH-RETARDATION AND LEAKY SCID PHENOTYPE OF KU70-DEFICIENT MICE

Ku70, Ku80, and DNA-PKcs are subunits of the DNA-dependent protein kin ase (DNA-PK), an enzyme implicated in DNA double-stranded break repair and V(D)J recombination. Our Ku70-deficient mice were about 50% the s ize of control littermates, and their fibroblasts were ionizing radiat ion sensitive and displayed premature senescence associated with the a ccumulation of nondividing cells. Ku70-deficient mice lacked mature B cells or serum immunoglobulin but, unexpectedly, reproducibly develope d small populations of thymic and peripheral alpha/beta T lineage cell s and had a significant incidence of thymic lymphomas. In association with B and T cell developmental defects, Ku70-deficient cells were sev erely impaired for joining of V(D)J coding and recombination signal se quences. These unanticipated features of the Ku70-deficient phenotype with respect to lymphocyte development and V(D)J recombination may ref lect differential functions of the three DNA-PK components.