title: Not All SCID Pigs Are Created Equally: Two Independent Mutations in the Artemis Gene Cause SCID in Pigs.
abstract: Mutations in >30 genes are known to result in impairment of the adaptive immune system, causing a group of disorders collectively known as SCID. SCID disorders are split into groups based on their presence and/or functionality of B, T, and NK cells. Piglets from a line of Yorkshire pigs at Iowa State University were shown to be affected by T(-)B(-)NK(+) SCID, representing, to our knowledge, the first example of naturally occurring SCID in pigs. In this study, we present evidence for two spontaneous mutations as the molecular basis for this SCID phenotype. Flow cytometry analysis of thymocytes showed an increased frequency of immature T cells in SCID pigs. Fibroblasts from these pigs were more sensitive to ionizing radiation than non-SCID piglets, eliminating the RAG1 and RAG2 genes. Genetic and molecular analyses showed that two mutations were present in the Artemis gene, which in the homozygous or compound heterozygous state cause the immunodeficient phenotype. Rescue of SCID fibroblast radiosensitivity by human Artemis protein demonstrated that the identified Artemis mutations are the direct cause of this cellular phenotype. The work presented in the present study reveals two mutations in the Artemis gene that cause T(-)B(-)NK(+) SCID in pigs. The SCID pig can be an important biomedical model, but these mutations would be undesirable in commercial pig populations. The identified mutations and associated genetic tests can be used to address both of these issues.
authors: Department of Animal Sciences, Iowa State University, Ames, IA 50011;
authors: Emily H
authors: EH
authors: Waide
authors: Department of Animal Sciences, Iowa State University, Ames, IA 50011;
authors: Jack C M
authors: JC
authors: Dekkers
authors: Department of Animal Sciences, Iowa State University, Ames, IA 50011;
authors: Jason W
authors: JW
authors: Ross
authors: College of Veterinary Medicine, Kansas State University, Manhattan, KS 66502; and.
authors: Raymond R R
authors: RR
authors: Rowland
authors: College of Veterinary Medicine, Kansas State University, Manhattan, KS 66502; and.
authors: Carol R
authors: CR
authors: Wyatt
authors: College of Veterinary Medicine, Kansas State University, Manhattan, KS 66502; and.
authors: Catherine L
authors: CL
authors: Ewen
authors: Department of Animal Sciences, Iowa State University, Ames, IA 50011;
authors: Alyssa B
authors: AB
authors: Evans
authors: Department of Animal Sciences, Iowa State University, Ames, IA 50011;
authors: Dinesh M
authors: DM
authors: Thekkoot
authors: Genesus, Inc., Oakville, Manitoba R0H 0Y0, Canada.
authors: Nicholas J
authors: NJ
authors: Boddicker
authors: Department of Animal Sciences, Iowa State University, Ames, IA 50011;
authors: Nick V L
authors: NV
authors: Serão
authors: Department of Animal Sciences, Iowa State University, Ames, IA 50011;
authors: N Matthew
authors: NM
authors: Ellinwood
authors: Department of Animal Sciences, Iowa State University, Ames, IA 50011; cktuggle@iastate.edu.
authors: Christopher K
authors: CK
authors: Tuggle
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics* / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002874:Chromosome Mapping; D045643:DNA Repair Enzymes / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D011836:Radiation Tolerance / Q000235:genetics; D017422:Sequence Analysis, DNA; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology*; D034421:Sus scrofa; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D009687:Nuclear Proteins; D045643:DNA Repair Enzymes