Generation of knockout rabbits with X-linked severe combined immunodeficiency (X-SCID) using CRISPR/Cas9
Generation of knockout rabbits with X-linked severe combined immunodeficiency (X-SCID) using CRISPR/Cas9
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DOI：
10.1038/s41598-020-66780-6
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发表时间：
2020-06-19
影响因子：
4.6
通讯作者：
Nishida, Kohji
中科院分区：
文献类型：
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作者：
Hashikawa, Yoshiko;Hayashi, Ryuhei;Nishida, Kohji
严重免疫缺陷小鼠被广泛用于检测人体和动物体内的细胞行为。然而，老鼠寿命短，体型小；而大型动物需要特定的大型设备。兔通常也被用作实验模型，比小鼠或大鼠更大，易于操作，适合长期观察和临床前研究。在这里，我们试图通过针对IL2RG的CRISPR/Cas9系统来培育和维持稳定的X连锁严重联合免疫缺陷(X-SCID)兔品系。因此，X-SCID兔表现出免疫缺陷的表型，包括T和B细胞的丢失和胸腺发育不良。此外，与野生型对照相比，这些兔在同种异体皮肤组织移植中表现出更高的植入率。X-SCID兔至少可以稳定维持4代。这些结果表明，X-SCID兔是用于严重免疫缺陷非啮齿动物模型的有效动物。
Severe immunodeficient mice are widely used to examine human and animal cells behaviour in vivo. However, mice are short-lived and small in size; while large animals require specific large-scale equipment. Rabbits are also commonly employed as experimental models and are larger than mice or rats, easy to handle, and suitable for long-term observational and pre-clinical studies. Herein, we sought to develop and maintain stable strains of rabbits with X-linked severe combined immunodeficiency (X-SCID) via the CRISPR/Cas9 system targeting Il2rg. Consequently, X-SCID rabbits presented immunodeficient phenotypes including the loss of T and B cells and hypoplasia of the thymus. Further, these rabbits exhibited a higher success rate with engraftments upon allogeneic transplantation of skin tissue than did wild type controls. X-SCID rabbits could be stably maintained for a minimum of four generations. These results indicate that X-SCID rabbits are effective animals for use in a non-rodent model of severe immunodeficiency.