Yu Yun, Zhang Nan, Dong Xianxiang, Fan Nan, Wang Lei, Xu Yuhui, Chen Huan, Duan Weigang
The Department of Pharmacology, School of Basic Medicine, Kunming Medical University, Kunming, Yunnan, China.
Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, School of Basic Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, China.
PeerJ. 2020 Apr 27;8:e8971. doi: 10.7717/peerj.8971. eCollection 2020.
Urate oxidase (uricase, Uox) is a big obstacle for scientists to establish stable animal models for studying hyperuricemia and associated disorders. Due to the low survival rate of uricase-deficient mice, we generated a Uox-knockout model animal from Sprague Dawley (SD) rats using the CRISPR/Cas9 technique by deleting exons 2 to 4 of the Uox gene. The uricase-deficient rats were named "Kunming-DY rats", and were apparently healthy with more than a 95% survival up to one year. The male rats' serum uric acid (SUA) increased to 48.3 ± 19.1 µg/ml, significantly higher than those of wild-type rats. Some indexes of the blood fat like total triglyceride, low density lipoprotein, and renal function indexes including blood urea nitrogen and serum creatinine were significantly different from those of wild-type rats, however, all the indexes were close to or in normal ranges. Histological renal changes including mild glomerular/tubular lesions were observed in these uricase-deficient rats. Thus, "Kunming-DY rats" with stable uricase-deficiency were successfully established and are an alternative model animal to study hyperuricemia and associated diseases mimicking human conditions.
尿酸氧化酶（尿酸酶，Uox）是科学家建立用于研究高尿酸血症及相关疾病的稳定动物模型的一大障碍。由于尿酸酶缺陷小鼠的存活率较低，我们利用CRISPR/Cas9技术，通过删除Uox基因的第2至4外显子，从Sprague Dawley（SD）大鼠中构建了一种Uox基因敲除模型动物。这种尿酸酶缺陷大鼠被命名为“昆明-DY大鼠”，它们看起来健康，在长达一年的时间里存活率超过95%。雄性大鼠的血清尿酸（SUA）升至48.3±19.1µg/ml，显著高于野生型大鼠。一些血脂指标如总甘油三酯、低密度脂蛋白，以及肾功能指标如血尿素氮和血清肌酐，与野生型大鼠有显著差异，不过所有指标都接近或处于正常范围。在这些尿酸酶缺陷大鼠中观察到了包括轻度肾小球/肾小管病变在内的肾脏组织学变化。因此，成功建立了具有稳定尿酸酶缺陷的“昆明-DY大鼠”，它们是一种替代模型动物，可用于研究模拟人类情况的高尿酸血症及相关疾病。
