Equine SCID: mechanistic analysis and comparison with murine SCID.
V(D)J rearrangement is the molecular mechanism by which an almost limitless number of unique immune receptors is generated. V(D)J rearrangement involves two DNA breaks and religations resulting in two DNA joints; coding and signal joints. If V(D)J recombination is impaired (as in murine SCID (C.B-17 mouse] or RAG [Recombinase Activating Genes) deficient mice), B lymphocyte and T lymphocyte development is blocked and severe immunodeficiency results. The first animal model of SCID was reported in Arabian foals in 1973. Recently we demonstrated that the mechanistic defect in SCID foals is V(D)J recombination. However, the impairment of V(D)J recombination in SCID foals is phenotypically distinct from SCID mice in that both signal and coding joint ligation are impaired. Furthermore, though equine SCID and murine SCID have definite phenotypic differences, both defects are likely to be the result of defective expression of the catalytic subunit of the DNA-dependent protein kinase.
Leber
R
R
Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Wiler
R
R
Perryman
L E
LE
Meek
K
K
D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D004247:DNA / Q000737:chemistry; D004587:Electrophoresis, Agar Gel / Q000662:veterinary; D005347:Fibroblasts / Q000737:chemistry / Q000276:immunology; D005786:Gene Expression Regulation; D015321:Gene Rearrangement / Q000235:genetics* / Q000276:immunology; D006734:Horse Diseases / Q000235:genetics* / Q000276:immunology; D006736:Horses; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011494:Protein Kinases / Q000032:analysis / Q000235:genetics; D012376:Rodent Diseases / Q000235:genetics* / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000662:veterinary*
D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D004247:DNA; D011494:Protein Kinases