Recombination activating gene-2 null severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently

// Yun-Jung Choi 1 , EunSu Kim 1 , Abu Musa Md Talimur Reza 1 , Kwonho Hong 1 , Hyuk Song 1 , Chankyu Park 1 , Seong-Keun Cho 2 , Kiho Lee 3 , Randall S. Prather 4 and Jin-Hoi Kim 1 1 Department of Stem Cell and Regenerative Biotechnology, Humanized Pig Research Center (SRC), Konkuk University, Seoul, Republic of Korea 2 Department of Animal Science, Pusan National University, Miryang, Gyeongnam, Republic of Korea 3 Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA, USA 4 Division of Animal Science, University of Missouri-Columbia, Columbia, MO, USA Correspondence to: Jin-Hoi Kim, email: // Keywords : severe combined immunodeficient, SCID, recombination activating gene-2, RAG-2, Talen, Immunology and Microbiology Section, Immune response, Immunity Received : June 22, 2017 Accepted : August 23, 2017 Published : September 02, 2017 Abstract 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.