Il2rg gene-targeted severe combined immunodeficiency pigs |
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| Authors: | Suzuki Shunichi Iwamoto Masaki Saito Yoriko Fuchimoto Daiichiro Sembon Shoichiro Suzuki Misae Mikawa Satoshi Hashimoto Michiko Aoki Yuki Najima Yuho Takagi Shinsuke Suzuki Nahoko Suzuki Emi Kubo Masanori Mimuro Jun Kashiwakura Yuji Madoiwa Seiji Sakata Yoichi Perry Anthony C F Ishikawa Fumihiko Onishi Akira |
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| Institution: | Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan. |
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| Abstract: | 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. |
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