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Browsing by Author "Song, Hyuk"

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    Partial loss of interleukin 2 receptor gamma function in pigs provides mechanistic insights for the study of human immunodeficiency syndrome
    Choi, Yun-Jung; Lee, Kiho; Park, Woo-Jin; Kwon, Deug-Nam; Park, Chankyu; Do, Jeong Tae; Song, Hyuk; Cho, Seong-Keun; Park, Kwang-Wook; Brown, Alana N.; Samuel, Melissa S.; Murphy, Clifton N.; Prather, Randall S.; Kim, Jin-Hoi (Impact Journals, 2016-08-09)
    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+/Δ69-368 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.
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    Recombination activating gene-2(null) severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently
    Choi, Yun-Jung; Kim, EunSu; Reza, Abu Musa Md Talimur; Hong, Kwonho; Song, Hyuk; Park, Chankyu; Cho, Seong-Keun; Lee, Kiho; Prather, Randall S.; Kim, Jin-Hoi (2017-09-19)
    This study comparatively investigated the transcriptional, physiological, and phenotypic differences of the immune disorder between severe combined immunodeficient (SCID) mouse and pig models. We discovered that the recombination activating gene-2 (Rag-2) SCID mice, but not RAG-2 SCID pigs, showed intense, infrequent, and mild cluster of CD3(+)-, CD4(+)-, and CD8(+) signals respectively, suggesting that distinct species-specific effects exist. Furthermore, the expression of six relevant genes (NFATC1, CD79B, CD2, BLNK, FOXO1, and CD40) was more downregulated than that in the Rag-2 SCID mice, which provides a partial rationale for the death of T/B cells in the lymphoid organs of RAG-2 SCID pigs but not in Rag-2 SCID mice. Further, NK cell maturation-related gene expression was significantly lower in RAG-2 SCID pigs than in Rag-2 SCID mice. Consistently, the RAG-2 SCID pigs, but not Rag-2 SCID mice, developed human induced pluripotent stem cell-derived teratomas that were the same as those of perforin/Rag-2 SCID mice. Therefore, these unexpected findings indicate the superiority of RAG-2 SCID pigs over Rag-2 SCID mice as a suitable model for investigating human diseases.