Il2rg gene-targeted severe combined immunodeficiency pigs

S. Suzuki; M. Iwamoto; Y. Saito; D. Fuchimoto; S. Sembon; M. Suzuki; S. Mikawa; M. Hashimoto; Y. Aoki; Y. Najima; S. Takagi; N. Suzuki; E. Suzuki; M. Kubo; J. Mimuro; Y. Kashiwakura; S. Madoiwa; Y. Sakata; Anthony C F Perry; F. Ishikawa; A. Onishi

doi:10.1016/j.stem.2012.04.021

Il2rg gene-targeted severe combined immunodeficiency pigs

S. Suzuki, M. Iwamoto, Y. Saito, D. Fuchimoto, S. Sembon, M. Suzuki, S. Mikawa, M. Hashimoto, Y. Aoki, Y. Najima, S. Takagi, N. Suzuki, E. Suzuki, M. Kubo, J. Mimuro, Y. Kashiwakura, S. Madoiwa, Y. Sakata, Anthony C F Perry, F. IshikawaA. Onishi

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

124 Citations (SciVal)

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.

Original language	English
Pages (from-to)	753-758
Number of pages	6
Journal	Cell Stem Cell
Volume	10
Issue number	6
Early online date	12 Jun 2012
DOIs	https://doi.org/10.1016/j.stem.2012.04.021
Publication status	Published - 14 Jun 2012

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10.1016/j.stem.2012.04.021

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Suzuki, S., Iwamoto, M., Saito, Y., Fuchimoto, D., Sembon, S., Suzuki, M., Mikawa, S., Hashimoto, M., Aoki, Y., Najima, Y., Takagi, S., Suzuki, N., Suzuki, E., Kubo, M., Mimuro, J., Kashiwakura, Y., Madoiwa, S., Sakata, Y., Perry, A. C. F., ... Onishi, A. (2012). Il2rg gene-targeted severe combined immunodeficiency pigs. Cell Stem Cell, 10(6), 753-758. https://doi.org/10.1016/j.stem.2012.04.021

Suzuki, S, Iwamoto, M, Saito, Y, Fuchimoto, D, Sembon, S, Suzuki, M, Mikawa, S, Hashimoto, M, Aoki, Y, Najima, Y, Takagi, S, Suzuki, N, Suzuki, E, Kubo, M, Mimuro, J, Kashiwakura, Y, Madoiwa, S, Sakata, Y, Perry, ACF, Ishikawa, F & Onishi, A 2012, 'Il2rg gene-targeted severe combined immunodeficiency pigs', Cell Stem Cell, vol. 10, no. 6, pp. 753-758. https://doi.org/10.1016/j.stem.2012.04.021

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title = "Il2rg gene-targeted severe combined immunodeficiency pigs",

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.",

author = "S. Suzuki and M. Iwamoto and Y. Saito and D. Fuchimoto and S. Sembon and M. Suzuki and S. Mikawa and M. Hashimoto and Y. Aoki and Y. Najima and S. Takagi and N. Suzuki and E. Suzuki and M. Kubo and J. Mimuro and Y. Kashiwakura and S. Madoiwa and Y. Sakata and Perry, {Anthony C F} and F. Ishikawa and A. Onishi",

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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.

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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.

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Il2rg gene-targeted severe combined immunodeficiency pigs

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Mammalian Sperm-borne DNA Binding Proteins

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Il2rg gene-targeted severe combined immunodeficiency pigs

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Mammalian Sperm-borne DNA Binding Proteins

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