Uox-flox Mouse

Uox, also known as urate oxidase, is an enzyme that metabolizes poorly-soluble uric acid (UA) to highly-soluble allantoin. Most mammals maintain normal serum uric acid levels via Uox. This process is crucial in purine metabolism pathways [4].

Uox-knockout (KO) mouse models have been widely used to study the role of Uox. Uox-KO mice spontaneously develop hyperuricemia, which is associated with multiple complications such as severe renal insufficiency, hypertension, left-ventricular remodeling, aortic endothelial dysfunction, hepatic steatosis, hyperglycemia, and hypercholesteremia [3]. These mice also exhibit systemic inflammation, impairment of intestinal integrity, and dysregulation of amino acids transportation that impacts serum uric acid level and CD4+ Th17-driven inflammation [1]. Additionally, in Urat1-Uox double-knockout (DKO) mice, which serve as models for hereditary renal hypouricemia type 1 (RHUC1), there are uricosuric effects, elevated renal injury markers, and increased NLRP3 inflammasome activity [2,5].

In conclusion, Uox is essential for maintaining normal uric acid metabolism. The study of Uox-KO and related double-knockout mouse models has significantly contributed to understanding the pathophysiology of hyperuricemia, gout, renal hypouricemia, and associated comorbidities, providing insights into potential therapeutic strategies for these diseases.