title: Partial loss of interleukin 2 receptor gamma function in pigs provides mechanistic insights for the study of human immunodeficiency syndrome.
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.
authors.affiliation: Animal Biotechnology to Stem Cell and Regenerative Biotechnology, Humanized Pig Research Center (SRC), Konkuk University, Seoul, Republic of Korea.
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA, USA.|Division of Animal Science, National Swine Resource and Research Center, University of Missouri, Columbia, MO, USA.
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.affiliation: Animal Biotechnology to Stem Cell and Regenerative Biotechnology, Humanized Pig Research Center (SRC), Konkuk University, Seoul, Republic of Korea.
authors.forename: Woo-Jin
authors.initials: WJ
authors.lastname: Park
authors.affiliation: Animal Biotechnology to Stem Cell and Regenerative Biotechnology, Humanized Pig Research Center (SRC), Konkuk University, Seoul, Republic of Korea.
authors.forename: Deug-Nam
authors.initials: DN
authors.lastname: Kwon
authors.affiliation: Animal Biotechnology to Stem Cell and Regenerative Biotechnology, Humanized Pig Research Center (SRC), Konkuk University, Seoul, Republic of Korea.
authors.forename: Chankyu
authors.initials: C
authors.lastname: Park
authors.affiliation: Animal Biotechnology to Stem Cell and Regenerative Biotechnology, Humanized Pig Research Center (SRC), Konkuk University, Seoul, Republic of Korea.
authors.forename: Jeong Tae
authors.initials: JT
authors.lastname: Do
authors.affiliation: Animal Biotechnology to Stem Cell and Regenerative Biotechnology, Humanized Pig Research Center (SRC), Konkuk University, Seoul, Republic of Korea.
authors.forename: Hyuk
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Animal Science, Pusan National University, Miryang, Gyeongnam, Republic of Korea.
authors.forename: Seong-Keun
authors.initials: SK
authors.lastname: Cho
authors.affiliation: Department of Animal Science and Technology, Sunchon National University, Suncheon, Jeonnam, Republic of Korea.
authors.forename: Kwang-Wook
authors.initials: KW
authors.lastname: Park
authors.affiliation: Division of Animal Science, National Swine Resource and Research Center, University of Missouri, Columbia, MO, USA.|National Swine Resource and Research Center, University of Missouri, Columbia, MO, USA.
authors.forename: Alana N
authors.initials: AN
authors.lastname: Brown
authors.affiliation: Division of Animal Science, National Swine Resource and Research Center, University of Missouri, Columbia, MO, USA.|National Swine Resource and Research Center, University of Missouri, Columbia, MO, USA.
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Samuel
authors.affiliation: Division of Animal Science, National Swine Resource and Research Center, University of Missouri, Columbia, MO, USA.|National Swine Resource and Research Center, University of Missouri, Columbia, MO, USA.
authors.forename: Clifton N
authors.initials: CN
authors.lastname: Murphy
authors.affiliation: Division of Animal Science, National Swine Resource and Research Center, University of Missouri, Columbia, MO, USA.|National Swine Resource and Research Center, University of Missouri, Columbia, MO, USA.
authors.forename: Randall S
authors.initials: RS
authors.lastname: Prather
authors.affiliation: Animal Biotechnology to Stem Cell and Regenerative Biotechnology, Humanized Pig Research Center (SRC), Konkuk University, Seoul, Republic of Korea.
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency* / Q000276:immunology; D016511:Severe Combined Immunodeficiency; D013552:Swine
chemical_list: D053631:Interleukin Receptor Common gamma Subunit
keywords: IL2RG; Pathology Section; TALEN; X-SCID; immunodeficiency; somatic cell nuclear transfer