Il2rg gene-targeted severe combined immunodeficiency pigs.
A porcine model of severe combined immunodeficiency (SCID) promises to facilitate human cancer studies, the humanization of tissue for xenotransplantation, and the evaluation of stem cells for clinical therapy, but SCID pigs have not been described. We report here the generation and preliminary evaluation of a porcine SCID model. Fibroblasts containing a targeted disruption of the X-linked interleukin-2 receptor gamma chain gene, Il2rg, were used as donors to generate cloned pigs by serial nuclear transfer. Germline transmission of the Il2rg deletion produced healthy Il2rg(+/-) females, while Il2rg(-/Y) males were athymic and exhibited markedly impaired immunoglobulin and T and NK cell production, robustly recapitulating human SCID. Following allogeneic bone marrow transplantation, donor cells stably integrated in Il2rg(-/Y) heterozygotes and reconstituted the Il2rg(-/Y) lymphoid lineage. The SCID pigs described here represent a step toward the comprehensive evaluation of preclinical cellular regenerative strategies.
Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan.
Shunichi
S
Suzuki
Prime Tech Ltd., Tsuchiura, Ibaraki 300-0841, Japan.
Masaki
M
Iwamoto
Research Unit for Human Disease Model, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
Yoriko
Y
Saito
Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan.
Daiichiro
D
Fuchimoto
Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan.
Shoichiro
S
Sembon
Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan.
Misae
M
Suzuki
Animal Genome Research Unit, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan.
Satoshi
S
Mikawa
Prime Tech Ltd., Tsuchiura, Ibaraki 300-0841, Japan.
Michiko
M
Hashimoto
Research Unit for Human Disease Model, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
Yuki
Y
Aoki
Research Unit for Human Disease Model, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
Yuho
Y
Najima
Research Unit for Human Disease Model, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
Shinsuke
S
Takagi
Research Unit for Human Disease Model, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
Nahoko
N
Suzuki
Laboratory of Mammalian Molecular Embryology, RIKEN Research Center for Developmental Biology, Kobe 650-0047, Japan.
Emi
E
Suzuki
Center for Animal Disease Control and Prevention, National Institute of Animal Health, Tsukuba, Ibaraki 305-0856, Japan.
Masanori
M
Kubo
Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi-ken 329-0498, Japan.
Jun
J
Mimuro
Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi-ken 329-0498, Japan.
Yuji
Y
Kashiwakura
Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi-ken 329-0498, Japan.
Seiji
S
Madoiwa
Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi-ken 329-0498, Japan.
Yoichi
Y
Sakata
Laboratory of Mammalian Molecular Embryology, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Anthony C F
ACF
Perry
Research Unit for Human Disease Model, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan. Electronic address: f_ishika@rcai.riken.jp.
Fumihiko
F
Ishikawa
Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan. Electronic address: onishi@affrc.go.jp.
Akira
A
Onishi
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D018390:Gene Targeting; D015316:Genetic Therapy; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D053631:Interleukin Receptor Common gamma Subunit