EQUINE SCID - MECHANISTIC ANALYSIS AND COMPARISON WITH MURINE SCID

V(D)J rearrangement is the molecular mechanism by which an almost limi tless number of unique immune receptors is generated. V(D)J rearrangem ent involves two DNA breaks and religations - resulting in two DNA joi nts; coding and signal joints. If V(D)J recombination is impaired las in murine SCID (C.B-17 mouse] or RAG [Recombinase Activating Genes) de ficient mice), B lymphocyte and T lymphocyte development is blocked an d severe immunodeficiency results. The first animal model of SCID was reported in Arabian foals in 1973. Recently we demonstrated that the m echanistic defect in SCID foals is V(D)J recombination. However, the i mpairment of V(D)J recombination in SCID foals is phenotypically disti nct from SCID mice in that both signal and coding joint ligation are i mpaired. Furthermore, though equine SCID and murine SCID have definite phenotypic differences, both defects are likely to be the result of d efective expression of the catalytic subunit of the DNA-dependent prot ein kinase. (C) 1998 Elsevier Science B.V. All rights reserved.