Uricase-deficient rat is generated with CRISPR/Cas9 technique

Abstract

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.