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 infinite 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 recombinase most likely consists of both lymphoid-specific factors and ubiquitously 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 foals is required for (i) V(D)J recombination, (ii) resistance to ionizing radiation, and (iii) DNA-dependent protein kinase activity.
Wiler
R
R
Department of Internal Medicine, Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Leber
R
R
Moore
B B
BB
VanDyk
L F
LF
Perryman
L E
LE
Meek
K
K
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004254:DNA Nucleotidyltransferases / Q000235:genetics*; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000528:radiation effects; D015321:Gene Rearrangement; D005808:Genes, Recessive; D018398:Homeodomain Proteins; D006734:Horse Diseases / Q000235:genetics*; D006736:Horses; D015151:Immunoblotting; D051379:Mice; D016513:Mice, SCID / Q000235:genetics; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics; D011995:Recombination, Genetic; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000662:veterinary*; D045567:VDJ Recombinases
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D011506:Proteins; C064658:RAG-1 protein; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases