Suzuki Shunichi, Iwamoto Masaki, Hashimoto Michiko, Suzuki Misae, Nakai Michiko, Fuchimoto Daiichiro, Sembon Shoichiro, Eguchi-Ogawa Tomoko, Uenishi Hirohide, Onishi Akira
Transgenic Pig Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan.
Prime Tech Ltd., Tsuchiura, Ibaraki 300-0841, Japan.
Vet Immunol Immunopathol. 2016 Oct 1;178:37-49. doi: 10.1016/j.vetimm.2016.06.011. Epub 2016 Jun 30.
Pigs with severe combined immunodeficiency (SCID) are versatile animal models for human medical research because of their biological similarities to humans, suitable body size, and longevity for practical research. SCID pigs with defined mutation(s) can be an invaluable tool for research on porcine immunity. In this study, we produced RAG2-knockout pigs via somatic cell nuclear transfer and analyzed their phenotype. The V(D)J recombination processes were confirmed as being inactivated. They consistently lacked mature T and B cells but had substantial numbers of cells considered to be T- or B-cell progenitors as well as NK cells. They also lacked thymic medulla and lymphoid aggregations in the spleen, mesenteric lymph nodes, and ileal Peyer's patches. We showed more severe immunological defects in the RAG2 and IL2RG double-knockout pig through this study. Thus, SCID pigs could be promising animal models not only for translational medical research but also for immunological studies of pigs themselves.
重度联合免疫缺陷（SCID）猪是人类医学研究中通用的动物模型，因为它们在生物学上与人类相似，体型合适，且寿命足以满足实际研究需求。具有特定突变的SCID猪对于猪免疫研究而言可能是一种非常有价值的工具。在本研究中，我们通过体细胞核移植制备了RAG2基因敲除猪，并分析了它们的表型。V（D）J重组过程被证实处于失活状态。它们始终缺乏成熟的T细胞和B细胞，但有大量被认为是T或B细胞祖细胞的细胞以及自然杀伤细胞（NK细胞）。它们还缺乏胸腺髓质以及脾脏、肠系膜淋巴结和回肠派尔集合淋巴结中的淋巴集结。通过本研究，我们发现RAG2和IL2RG双基因敲除猪存在更严重的免疫缺陷问题。因此，SCID猪不仅可能成为转化医学研究的有前景的动物模型，也可能成为猪自身免疫学研究的有前景的动物模型。
