TY - JOUR
T1 - Il2rg gene-targeted severe combined immunodeficiency pigs
AU - Suzuki, S.
AU - Iwamoto, M.
AU - Saito, Y.
AU - Fuchimoto, D.
AU - Sembon, S.
AU - Suzuki, M.
AU - Mikawa, S.
AU - Hashimoto, M.
AU - Aoki, Y.
AU - Najima, Y.
AU - Takagi, S.
AU - Suzuki, N.
AU - Suzuki, E.
AU - Kubo, M.
AU - Mimuro, J.
AU - Kashiwakura, Y.
AU - Madoiwa, S.
AU - Sakata, Y.
AU - Perry, Anthony C F
AU - Ishikawa, F.
AU - Onishi, A.
PY - 2012/6/14
Y1 - 2012/6/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84862560337&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1016/j.stem.2012.04.021
U2 - 10.1016/j.stem.2012.04.021
DO - 10.1016/j.stem.2012.04.021
M3 - Article
VL - 10
SP - 753
EP - 758
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 6
ER -
