Cell Stem Cell：日成功培育出无免疫力猪

Il2rg Gene-Targeted Severe Combined Immunodeficiency Pigs

Shunichi Suzuki, Masaki Iwamoto, Yoriko Saito, Daiichiro Fuchimoto, Shoichiro Sembon, Misae Suzuki, Satoshi Mikawa, Michiko Hashimoto, Yuki Aoki, Yuho Najima, Shinsuke Takagi, Nahoko Suzuki, Emi Suzuki, Masanori Kubo, Jun Mimuro, Yuji Kashiwakura, Seiji Madoiwa, Yoichi Sakata, Anthony C.F. Perry, Fumihiko Ishikawa, Akira Onis

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.