Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-0901, Japan.
Prime Tech Ltd., Tsuchiura, Ibaraki 300-0841, Japan.
Cell Stem Cell. 2012 Jun 14;10(6):753-758. doi: 10.1016/j.stem.2012.04.021.
A porcine model of severe combined immunodeficiency (SCID) promises to facilitate human cancer studies, the humanization of tissue for xenotransplantation, and the evaluation of stem cells for clinical therapy, but SCID pigs have not been described. We report here the generation and preliminary evaluation of a porcine SCID model. Fibroblasts containing a targeted disruption of the X-linked interleukin-2 receptor gamma chain gene, Il2rg, were used as donors to generate cloned pigs by serial nuclear transfer. Germline transmission of the Il2rg deletion produced healthy Il2rg(+/-) females, while Il2rg(-/Y) males were athymic and exhibited markedly impaired immunoglobulin and T and NK cell production, robustly recapitulating human SCID. Following allogeneic bone marrow transplantation, donor cells stably integrated in Il2rg(-/Y) heterozygotes and reconstituted the Il2rg(-/Y) lymphoid lineage. The SCID pigs described here represent a step toward the comprehensive evaluation of preclinical cellular regenerative strategies.
严重联合免疫缺陷（SCID）猪模型有望促进人类癌症研究、组织异种移植的人源化以及临床治疗用干细胞的评估，但尚未有 SCID 猪的相关报道。本文报道了一种 SCID 猪模型的产生及初步评估。利用含有靶向破坏 X 连锁白细胞介素 2 受体 γ 链基因（Il2rg）的成纤维细胞作为供体，通过连续核移植生成克隆猪。Il2rg 缺失的生殖系传递产生了健康的 Il2rg(+/-)雌性，而 Il2rg(-/Y)雄性则为无胸腺，并且表现出明显的免疫球蛋白和 T 及 NK 细胞产生缺陷，有力地重现了人类 SCID。在进行异基因骨髓移植后，供体细胞在 Il2rg(-/Y)杂合子中稳定整合并重建了 Il2rg(-/Y)淋巴细胞系。本文描述的 SCID 猪代表了朝着全面评估临床前细胞再生策略迈出的一步。
