title: Generation and characterization of RAG2 knockout pigs as animal model for severe combined immunodeficiency.
abstract: Pigs with severe combined immunodeficiency (SCID) are versatile animal models for human medical research because of their biological similarities to humans, suitable body size, and longevity for practical research. SCID pigs with defined mutation(s) can be an invaluable tool for research on porcine immunity. In this study, we produced RAG2-knockout pigs via somatic cell nuclear transfer and analyzed their phenotype. The V(D)J recombination processes were confirmed as being inactivated. They consistently lacked mature T and B cells but had substantial numbers of cells considered to be T- or B-cell progenitors as well as NK cells. They also lacked thymic medulla and lymphoid aggregations in the spleen, mesenteric lymph nodes, and ileal Peyer's patches. We showed more severe immunological defects in the RAG2 and IL2RG double-knockout pig through this study. Thus, SCID pigs could be promising animal models not only for translational medical research but also for immunological studies of pigs themselves.
authors: Transgenic Pig Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan. Electronic address: shunsuzu@affrc.go.jp.
authors: Shunichi
authors: S
authors: Suzuki
authors: Prime Tech Ltd., Tsuchiura, Ibaraki 300-0841, Japan.
authors: Masaki
authors: M
authors: Iwamoto
authors: Prime Tech Ltd., Tsuchiura, Ibaraki 300-0841, Japan.
authors: Michiko
authors: M
authors: Hashimoto
authors: Transgenic Pig Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan.
authors: Misae
authors: M
authors: Suzuki
authors: Transgenic Pig Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan.
authors: Michiko
authors: M
authors: Nakai
authors: Transgenic Pig Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan.
authors: Daiichiro
authors: D
authors: Fuchimoto
authors: Transgenic Pig Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan.
authors: Shoichiro
authors: S
authors: Sembon
authors: Animal Genome Research Unit, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan.
authors: Tomoko
authors: T
authors: Eguchi-Ogawa
authors: Animal Genome Research Unit, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan; Animal Immune and Cell Biology Research Unit, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8634, Japan.
authors: Hirohide
authors: H
authors: Uenishi
authors: Transgenic Pig Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan; Laboratory of Animal Reproduction, Department of Animal Science and Resources, College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa 252-0880, Japan.
authors: Akira
authors: A
authors: Onishi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D055786:Gene Knockout Techniques / Q000379:methods / Q000662:veterinary*; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D054503:Lymphoid Progenitor Cells / Q000276:immunology / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D034421:Sus scrofa; D013552:Swine; D013553:Swine Diseases / Q000235:genetics* / Q000276:immunology* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D053631:Interleukin Receptor Common gamma Subunit; C064655:V(D)J recombination activating protein 2
keywords: Immunodeficient animal; Lymphogenesis; Pigs; RAG2