Irradiation-induced rescue of thymocyte differentiation and V(D)J recombination in mice lacking the catalytic subunit of DNA-dependent protein kinase

Scid mice express a truncated form of the catalytic subunit of the DNA-depe ndent protein kinase (DNA-PKcs) and are unable to properly rearrange their Ig and TCR genes, resulting in a severe combined immunodeficiency that is c haracterized by arrested differentiation of B and T lymphocytes, Treatment of scid mice with low doses of gamma irradiation rescues rearrangements at several TCR loci and promotes limited thymocyte differentiation. The machin ery responsible for sensing DNA damage and the mechanism by which irradiati on compensates for the scid defect in TCR recombination remain unknown. Bec ause DNA-PKcs is present in scid thymocytes, it may mediate some or all of the irradiation effects. To test this hypothesis, we examined the effects o f irradiation on DNA-PKcs-deficient (slip) mice. Our data provide the first evidence that DNA-PKcs is not required for limited rescue of thymocyte dif ferentiation or TCR rearrangements.