EQUINE SEVERE COMBINED IMMUNODEFICIENCY - A DEFECT IN V(D)J RECOMBINATION AND DNA-DEPENDENT PROTEIN-KINASE ACTIVITY

V(D)J rearrangement is the molecular mechanism by which an almost infi nite array of specific immune receptors are generated. Defects in this process result in profound immunodeficiency as is the case in the C.B -17 SCID mouse or in RAG-1 (recombination-activating gene 1) or RAG-2 deficient mice. It has recently become clear that the V(D)J recombinas e most likely consists of both lymphoid-specific factors and ubiquitou sly expressed components of the DNA double-strand break repair pathway . The deficit in SCID mice is in a factor that is required for both of these pathways. In this report, we show that the factor defective in the autosomal recessive severe combined immunodeficiency of Arabian fo als is required for (i) V(D)J recombination, (ii) resistance to ionizi ng radiation, and (iii) DNA-dependent protein kinase activity.