RAG1/2 knockout pigs with severe combined immunodeficiency

Research output: Contribution to journalArticlepeer-review

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RAG1/2 knockout pigs with severe combined immunodeficiency. / Huang, Jiao; Guo, Xiaogang; Fan, Nana; Song, Jun; Zhao, Bentian; Ouyang, Zhen; Liu, Zhaoming; Zhao, Yu; Yan, Quanmei; Yi, Xiaoling; Schambach, Axel; Frampton, Jonathan; Esteban, Miguel A; Yang, Dongshan; Yang, Huaqiang; Lai, Liangxue.

In: Journal of Immunology, Vol. 193, No. 3, 01.08.2014, p. 1496-503.

Research output: Contribution to journalArticlepeer-review

Harvard

Huang, J, Guo, X, Fan, N, Song, J, Zhao, B, Ouyang, Z, Liu, Z, Zhao, Y, Yan, Q, Yi, X, Schambach, A, Frampton, J, Esteban, MA, Yang, D, Yang, H & Lai, L 2014, 'RAG1/2 knockout pigs with severe combined immunodeficiency', Journal of Immunology, vol. 193, no. 3, pp. 1496-503. https://doi.org/10.4049/jimmunol.1400915

APA

Huang, J., Guo, X., Fan, N., Song, J., Zhao, B., Ouyang, Z., Liu, Z., Zhao, Y., Yan, Q., Yi, X., Schambach, A., Frampton, J., Esteban, M. A., Yang, D., Yang, H., & Lai, L. (2014). RAG1/2 knockout pigs with severe combined immunodeficiency. Journal of Immunology, 193(3), 1496-503. https://doi.org/10.4049/jimmunol.1400915

Vancouver

Huang J, Guo X, Fan N, Song J, Zhao B, Ouyang Z et al. RAG1/2 knockout pigs with severe combined immunodeficiency. Journal of Immunology. 2014 Aug 1;193(3):1496-503. https://doi.org/10.4049/jimmunol.1400915

Author

Huang, Jiao ; Guo, Xiaogang ; Fan, Nana ; Song, Jun ; Zhao, Bentian ; Ouyang, Zhen ; Liu, Zhaoming ; Zhao, Yu ; Yan, Quanmei ; Yi, Xiaoling ; Schambach, Axel ; Frampton, Jonathan ; Esteban, Miguel A ; Yang, Dongshan ; Yang, Huaqiang ; Lai, Liangxue. / RAG1/2 knockout pigs with severe combined immunodeficiency. In: Journal of Immunology. 2014 ; Vol. 193, No. 3. pp. 1496-503.

Bibtex

@article{af5faaec4e2144c2b5b80a60faaccb1a,
title = "RAG1/2 knockout pigs with severe combined immunodeficiency",
abstract = "Pigs share many physiological, biochemical, and anatomical similarities with humans and have emerged as valuable large animal models for biomedical research. Considering the advantages in immune system resemblance, suitable size, and longevity for clinical practical and monitoring purpose, SCID pigs bearing dysfunctional RAG could serve as important experimental tools for regenerative medicine, allograft and xenograft transplantation, and reconstitution experiments related to the immune system. In this study, we report the generation and phenotypic characterization of RAG1 and RAG2 knockout pigs using transcription activator-like effector nucleases. Porcine fetal fibroblasts were genetically engineered using transcription activator-like effector nucleases and then used to provide donor nuclei for somatic cell nuclear transfer. We obtained 27 live cloned piglets; among these piglets, 9 were targeted with biallelic mutations in RAG1, 3 were targeted with biallelic mutations in RAG2, and 10 were targeted with a monoallelic mutation in RAG2. Piglets with biallelic mutations in either RAG1 or RAG2 exhibited hypoplasia of immune organs, failed to perform V(D)J rearrangement, and lost mature B and T cells. These immunodeficient RAG1/2 knockout pigs are promising tools for biomedical and translational research.",
keywords = "Anemia, Aplastic, Animals, DNA-Binding Proteins, Disease Models, Animal, Embryo Transfer, Female, Fibroblasts, Gene Knockout Techniques, Gene Targeting, Homeodomain Proteins, INDEL Mutation, Male, Primary Cell Culture, Recombination, Genetic, Severe Combined Immunodeficiency, Sus scrofa, Swine, Swine, Miniature",
author = "Jiao Huang and Xiaogang Guo and Nana Fan and Jun Song and Bentian Zhao and Zhen Ouyang and Zhaoming Liu and Yu Zhao and Quanmei Yan and Xiaoling Yi and Axel Schambach and Jonathan Frampton and Esteban, {Miguel A} and Dongshan Yang and Huaqiang Yang and Liangxue Lai",
note = "Copyright {\textcopyright} 2014 by The American Association of Immunologists, Inc.",
year = "2014",
month = aug,
day = "1",
doi = "10.4049/jimmunol.1400915",
language = "English",
volume = "193",
pages = "1496--503",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

RIS

TY - JOUR

T1 - RAG1/2 knockout pigs with severe combined immunodeficiency

AU - Huang, Jiao

AU - Guo, Xiaogang

AU - Fan, Nana

AU - Song, Jun

AU - Zhao, Bentian

AU - Ouyang, Zhen

AU - Liu, Zhaoming

AU - Zhao, Yu

AU - Yan, Quanmei

AU - Yi, Xiaoling

AU - Schambach, Axel

AU - Frampton, Jonathan

AU - Esteban, Miguel A

AU - Yang, Dongshan

AU - Yang, Huaqiang

AU - Lai, Liangxue

N1 - Copyright © 2014 by The American Association of Immunologists, Inc.

PY - 2014/8/1

Y1 - 2014/8/1

N2 - Pigs share many physiological, biochemical, and anatomical similarities with humans and have emerged as valuable large animal models for biomedical research. Considering the advantages in immune system resemblance, suitable size, and longevity for clinical practical and monitoring purpose, SCID pigs bearing dysfunctional RAG could serve as important experimental tools for regenerative medicine, allograft and xenograft transplantation, and reconstitution experiments related to the immune system. In this study, we report the generation and phenotypic characterization of RAG1 and RAG2 knockout pigs using transcription activator-like effector nucleases. Porcine fetal fibroblasts were genetically engineered using transcription activator-like effector nucleases and then used to provide donor nuclei for somatic cell nuclear transfer. We obtained 27 live cloned piglets; among these piglets, 9 were targeted with biallelic mutations in RAG1, 3 were targeted with biallelic mutations in RAG2, and 10 were targeted with a monoallelic mutation in RAG2. Piglets with biallelic mutations in either RAG1 or RAG2 exhibited hypoplasia of immune organs, failed to perform V(D)J rearrangement, and lost mature B and T cells. These immunodeficient RAG1/2 knockout pigs are promising tools for biomedical and translational research.

AB - Pigs share many physiological, biochemical, and anatomical similarities with humans and have emerged as valuable large animal models for biomedical research. Considering the advantages in immune system resemblance, suitable size, and longevity for clinical practical and monitoring purpose, SCID pigs bearing dysfunctional RAG could serve as important experimental tools for regenerative medicine, allograft and xenograft transplantation, and reconstitution experiments related to the immune system. In this study, we report the generation and phenotypic characterization of RAG1 and RAG2 knockout pigs using transcription activator-like effector nucleases. Porcine fetal fibroblasts were genetically engineered using transcription activator-like effector nucleases and then used to provide donor nuclei for somatic cell nuclear transfer. We obtained 27 live cloned piglets; among these piglets, 9 were targeted with biallelic mutations in RAG1, 3 were targeted with biallelic mutations in RAG2, and 10 were targeted with a monoallelic mutation in RAG2. Piglets with biallelic mutations in either RAG1 or RAG2 exhibited hypoplasia of immune organs, failed to perform V(D)J rearrangement, and lost mature B and T cells. These immunodeficient RAG1/2 knockout pigs are promising tools for biomedical and translational research.

KW - Anemia, Aplastic

KW - Animals

KW - DNA-Binding Proteins

KW - Disease Models, Animal

KW - Embryo Transfer

KW - Female

KW - Fibroblasts

KW - Gene Knockout Techniques

KW - Gene Targeting

KW - Homeodomain Proteins

KW - INDEL Mutation

KW - Male

KW - Primary Cell Culture

KW - Recombination, Genetic

KW - Severe Combined Immunodeficiency

KW - Sus scrofa

KW - Swine

KW - Swine, Miniature

U2 - 10.4049/jimmunol.1400915

DO - 10.4049/jimmunol.1400915

M3 - Article

C2 - 24973446

VL - 193

SP - 1496

EP - 1503

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -