title: Molecular pathology of severe combined immunodeficiency in mice, horses, and dogs.
abstract: Severe combined immunodeficiency (SCID) is an inherited disorder of humans, mice, horses, and dogs, in which affected individuals are incapable of generating antigen-specific immune responses. It occurs when lymphocyte precursors fail to differentiate into mature lymphocytes because of mutations within recombinase-activating genes 1 and 2 or within the genes encoding deoxyribonucleic acid (DNA)-dependent protein kinase (DNA-PK). It also occurs when differentiated lymphocytes are incapable of completing signal transduction pathways because of defects in cell surface receptors for interleukins (IL). A spontaneous mutation in DNA-PKcs of BALB/c mice results in SCID, as do experimentally induced mutations in RAG1 and RAG2. SCID in horses results from a spontaneous mutation in DNA-PKcs. Two molecular mechanisms account for SCID in dogs. Jack Russell Terriers have a mutation within the DNA-PKcs gene, whereas Cardigan Welsh Corgi and Basset Hound have different defects in the gene encoding the gamma chain that is common to the receptors for IL-2, -4, -7, -9, -15, and -21. The location of the mutation within target genes influences the spectrum of diseases observed in affected animals.
authors.affiliation: College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1601, USA. lance.perryman@colostate.edu.
authors.forename: L E
authors.initials: LE
authors.lastname: Perryman
mesh_terms: D000818:Animals; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D016654:Genes, RAG-1 / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D006734:Horse Diseases / Q000235:genetics*; D006736:Horses; D007142:Immunoglobulin gamma-Chains / Q000235:genetics; D008214:Lymphocytes / Q000473:pathology*; D051379:Mice; D009154:Mutation / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012376:Rodent Diseases / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000662:veterinary*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D007142:Immunoglobulin gamma-Chains; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases