The Wiskott-Aldrich syndrome (WAS) is a severe recessive X-linked immunodeficiency resulting from loss-of-function mutations in the WAS gene. Mouse is the only mammalian model used for investigation of WAS pathogenesis. However, the mouse model does not accurately recapitulate WAS clinical phenotypes, thus, limiting its application in WAS clinical research. Herein, we report the generation of WAS knockout (KO) rabbits via embryo co-injection of Cas9 mRNA and a pair of sgRNAs targeting exons 2 and 7. WAS KO rabbits exhibited many symptoms similar to those of WAS patients, including thrombocytopenia, bleeding tendency, infections, and reduced numbers of T cell in the spleen and peripheral blood. The WAS KO rabbit model provides a new valuable tool for preclinical trials of WAS treatment.

中文翻译：

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Wiskott-Aldrich 综合征兔模型的建立

Wiskott-Aldrich 综合征 (WAS) 是一种严重的隐性 X 连锁免疫缺陷，由 WAS 基因的功能丧失突变引起。小鼠是唯一用于研究 WAS 发病机制的哺乳动物模型。然而，小鼠模型不能准确地概括 WAS 临床表型，因此限制了其在 WAS 临床研究中的应用。在此，我们报告了通过胚胎共注射 Cas9 mRNA 和一对靶向外显子 2 和 7 的 sgRNA 产生 WAS 敲除 (KO) 兔。 WAS KO 兔表现出许多与 WAS 患者相似的症状，包括血小板减少症、出血倾向、感染以及脾脏和外周血中 T 细胞数量减少。WAS KO 兔模型为 WAS 治疗的临床前试验提供了一种新的有价值的工具。