Choi, Yun-JungLee, KihoPark, Woo-JinKwon, Deug-NamPark, ChankyuDo, Jeong TaeSong, HyukCho, Seong-KeunPark, Kwang-WookBrown, Alana N.Samuel, Melissa S.Murphy, Clifton N.Prather, Randall S.Kim, Jin-Hoi2018-01-152018-01-152016-08-091949-2553http://hdl.handle.net/10919/81772In 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+/Δ69-368 KO 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.50914 - 50926 (13) page(s)application/pdfenCreative Commons Attribution 3.0 UnportedOncologyCell BiologyIL2RGX-SCIDimmunodeficiencysomatic cell nuclear transferTALENPathology SectionCHAINCELLSLIVESTOCKKNOCKOUTGENESArticle - Refereedhttps://doi.org/10.18632/oncotarget.10812732