UOX Mouse Model

UOX KO mice are genetically modified models generated by knocking out the urate oxidase (Uox / Uricase) gene in mice using gene-editing technology, designed to simulate spontaneous hyperuricemia and its complications resulting from a lack of functional uricase in rodents. Heterozygotes (Uox+/-): Viable and fertile, with mildly elevated serum uric acid. Homozygotes (Uox−/−): Completely deficient in uricase, with serum uric acid reaching 10–12 times that of wild-type mice (approximately 420–650 μmol/L or higher); early ES cell homologous recombination versions show approximately 65% mortality within 4 weeks of age, whereas TALEN/CRISPR-optimized versions show approximately 40% viability beyond 60 weeks, though allopurinol maintenance is typically required to prolong survival.

Most mammals express UOX in the liver, which further breaks down uric acid into highly water-soluble allantoin for excretion; however, UOX became inactive during human evolution, leaving uric acid as the end product of purine metabolism and resulting in baseline blood uric acid levels higher than those of typical mice. Using homologous recombination to knock out the mouse Uox gene prevents hepatocytes from synthesizing functional uricase. Uric acid production remains normal while degradation is blocked → sustained elevation of serum uric acid → urate deposition in the renal interstitium/tubules → uric acid nephropathy, tubular dilation, interstitial fibrosis, and inflammatory infiltration; some strains are accompanied by comorbidities such as hypertension, glucose and lipid metabolism abnormalities, and non-alcoholic fatty liver disease (NAFLD).