Il2rg Gene-Targeted Severe Combined Immunodeficiency Pigs

被引：126

作者：

Suzuki, Shunichi ^{[3
]}

Iwamoto, Masaki ^{[5
]}

Saito, Yoriko ^{[1
]}

Fuchimoto, Daiichiro ^{[3
]}

Sembon, Shoichiro ^{[3
]}

Suzuki, Misae ^{[3
]}

Mikawa, Satoshi ^{[4
]}

Hashimoto, Michiko ^{[5
]}

Aoki, Yuki ^{[1
]}

Najima, Yuho ^{[1
]}

Takagi, Shinsuke ^{[1
]}

Suzuki, Nahoko ^{[1
]}

Suzuki, Emi ^{[2
]}

Kubo, Masanori ^{[6
]}

Mimuro, Jun ^{[7
]}

Kashiwakura, Yuji ^{[7
]}

Madoiwa, Seiji ^{[7
]}

Sakata, Yoichi ^{[7
]}

Perry, Anthony C. F. ^{[8
]}

Ishikawa, Fumihiko ^{[1
]}

Onishi, Akira ^{[3
]}

机构：

[1] RIKEN Res Ctr Allergy & Immunol, Res Unit Human Dis Model, Yokohama, Kanagawa 2300045, Japan

[2] RIKEN Res Ctr Dev Biol, Lab Mammalian Mol Embryol, Kobe, Hyogo 6500047, Japan

[3] Natl Inst Agrobiol Sci, Transgen Anim Res Ctr, Tsukuba, Ibaraki 3050901, Japan

[4] Natl Inst Agrobiol Sci, Anim Genome Res Unit, Tsukuba, Ibaraki 3050901, Japan

[5] Prime Tech Ltd, Tsuchiura, Ibaraki 3000841, Japan

[6] Natl Inst Anim Hlth, Ctr Anim Dis Control & Prevent, Tsukuba, Ibaraki 3050856, Japan

[7] Jichi Med Univ, Ctr Mol Med, Div Cell & Mol Med, Shimotsuke, Tochigi 3290498, Japan

[8] Univ Bath, Dept Biol & Biochem, Lab Mammalian Mol Embryol, Bath BA2 7AY, Avon, England

来源：

CELL STEM CELL | 2012年 / 10卷 / 06期

关键词：

INTERLEUKIN-2-RECEPTOR GAMMA-CHAIN; T-CELL PROLIFERATION; IL-2; RECEPTOR; BETA-CHAIN; FUNCTIONAL COMPONENT; CYTOPLASMIC DOMAINS; IMMUNE-SYSTEM; CLONED MICE; STEM-CELLS; EXPRESSION;

D O I：

10.1016/j.stem.2012.04.021

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：753 / 758

页数：6

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