Oncotarget

Research Papers: Pathology:

Partial loss of interleukin 2 receptor gamma function in pigs provides mechanistic insights for the study of human immunodeficiency syndrome

Yun-Jung Choi, Kiho Lee, Woo-Jin Park, Deug-Nam Kwon, Chankyu Park, Jeong Tae Do, Hyuk Song, Seong-Keun Cho, Kwang-Wook Park, Alana N. Brown, Melissa S. Samuel, Clifton N. Murphy, Randall S. Prather _ and Jin-Hoi Kim

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Oncotarget. 2016; 7:50914-50926. https://doi.org/10.18632/oncotarget.10812

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Abstract

Yun-Jung Choi1,*, Kiho Lee2,3,*, Woo-Jin Park1, Deug-Nam Kwon1, Chankyu Park1, Jeong Tae Do1, Hyuk Song1, Seong-Keun Cho5, Kwang-Wook Park6, Alana N. Brown3,4, Melissa S. Samuel3,4, Clifton N. Murphy3,4, Randall S. Prather3,4 and Jin-Hoi Kim1

1 Animal Biotechnology to Stem Cell and Regenerative Biotechnology, Humanized Pig Research Center (SRC), Konkuk University, Seoul, Republic of Korea

2 Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA, USA

3 Division of Animal Science, National Swine Resource and Research Center, University of Missouri, Columbia, MO, USA

4 National Swine Resource and Research Center, University of Missouri, Columbia, MO, USA

5 Department of Animal Science, Pusan National University, Miryang, Gyeongnam, Republic of Korea

6 Department of Animal Science and Technology, Sunchon National University, Suncheon, Jeonnam, Republic of Korea

* These authors have contributed equally to this work

Correspondence to:

Randall S. Prather, email:

Jin-Hoi Kim, email:

Keywords: IL2RG, X-SCID, immunodeficiency, somatic cell nuclear transfer, TALEN, Pathology Section

Received: May 08, 2016 Accepted: July 13, 2016 Published: July 24, 2016

Abstract

In this study, we described the phenotype of monoallelic interleukin 2 receptor gamma knockout (mIL2RG+/Δ69-368 KO) pigs. Approximately 80% of mIL2RG+/Δ69-368 KO pigs (8/10) were athymic, whereas 20% (2/10) presented a rudimentary thymus. The body weight of IL2RG+/Δ69-368KO pigs developed normally. Immunological analysis showed that mIL2RG+/Δ69-368 KO pigs possessed CD25+CD44- or CD25-CD44+ cells, whereas single (CD4 or CD8) or double (CD4/8) positive cells were lacking in mIL2RG+/Δ69-368 KO pigs. CD3+ cells in the thymus of mIL2RG+/Δ69-368 KO pigs contained mainly CD44+ cells and/or CD25+ cells, which included FOXP3+ cells. These observations demonstrated that T cells from mIL2RG+/Δ69-368 KO pigs were able to develop to the DN3 stage, but failed to transition toward the DN4 stage. Whole-transcriptome analysis of thymus and spleen, and subsequent pathway analysis revealed that a subset of genes differentially expressed following the loss of IL2RG might be responsible for both impaired T-cell receptor and cytokine-mediated signalling. However, comparative analysis of two mIL2RG+/Δ69-368 KO pigs revealed little variability in the down- and up-regulated gene sets. In conclusion, mIL2RG+/Δ69-368 KO pigs presented a T-B+NK- SCID phenotype, suggesting that pigs can be used as a valuable and suitable biomedical model for human SCID research.


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