CRISPR/Cas9 Mediated Deletion of the Uox Gene Generates a Mouse Model of Hyperuricemia with Multiple Complications.

ABSTRACT: Hyperuricemia is a common metabolic disorder with severe complications. We aimed to develop a mouse model for spontaneous hyperuricemia. Uox^-/- mouse model was generated on C57BL/6J background by deleting exon 2-4 of Uox using the CRISPR/Cas9 system. The prototypic Uox ^-/-mice had 5.5-fold increased serum uric acid (1351.04±276.58μmol/L) as compared to the wild type mice (P<0.0001), but died by 4 weeks. After allopurinol (3ug/g) intervention, they all survived > 8 weeks. The serum uric acid was 612.55±146.98μmol/L in the 8-week-old allopurinol-rescued Uox ^-/-mice, which manifested multiple complications including severe renal insufficiency, hypertension, left ventricular remodeling and systolic dysfunction, aortic endothelial dysfunction, hepatic steatosis

SUBMITTER: Zeng L 

PROVIDER: S-EPMC11635051 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature