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 & 1 others A. Onishi

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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.
Original languageEnglish
Pages (from-to)753-758
Number of pages6
JournalCell Stem Cell
Volume10
Issue number6
Early online date12 Jun 2012
DOIs
Publication statusPublished - 14 Jun 2012

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Severe Combined Immunodeficiency
Swine
Genes
Interleukin Receptor Common gamma Subunit
Heterologous Transplantation
Homologous Transplantation
Heterozygote
Cell- and Tissue-Based Therapy
Bone Marrow Transplantation
Natural Killer Cells
Immunoglobulins
Stem Cells
Fibroblasts
T-Lymphocytes
Neoplasms

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Suzuki, S., Iwamoto, M., Saito, Y., Fuchimoto, D., Sembon, S., Suzuki, M., ... 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

Il2rg gene-targeted severe combined immunodeficiency pigs. / 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, Anthony C F; Ishikawa, F.; Onishi, A.

In: Cell Stem Cell, Vol. 10, No. 6, 14.06.2012, p. 753-758.

Research output: Contribution to journalArticle

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
Suzuki S, Iwamoto M, Saito Y, Fuchimoto D, Sembon S, Suzuki M et al. Il2rg gene-targeted severe combined immunodeficiency pigs. Cell Stem Cell. 2012 Jun 14;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, Anthony C F ; Ishikawa, F. ; Onishi, A. / Il2rg gene-targeted severe combined immunodeficiency pigs. In: Cell Stem Cell. 2012 ; Vol. 10, No. 6. pp. 753-758.
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AU - Suzuki, M.

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AU - Madoiwa, S.

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AU - Onishi, A.

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