Hyperuricemia

UOX-KO mice exhibit markedly elevated serum uric acid from an early age, accompanied by increased CREA, BUN, and urinary uric acid levels. Renal histopathology further indicates the presence of spontaneous kidney injury and fibrosis.

(A–C) Changes in serum uric acid (UA), serum creatinine (CREA), and blood urea nitrogen (BUN) levels in the two groups of mice at different time points.(D) Representative H&E-stained kidney sections from the two groups at 4 weeks of age, showing more pronounced renal tissue injury in the UOX-KO group; colored arrows indicate representative pathological alterations.(E) Representative H&E-stained kidney sections from the two groups at 8 weeks of age, showing more pronounced renal tissue injury in the UOX-KO group; colored arrows indicate representative pathological alterations.(F) Quantitative analysis of renal pathological changes in the two groups at 4 and 8 weeks of age. Colored arrows indicate representative pathological alterations.(G) Representative Masson-stained kidney sections from the two groups at 4 weeks of age. (H) Representative Masson-stained kidney sections from the two groups at 8 weeks of age, used to assess renal interstitial collagen deposition and fibrotic changes. (I) Quantification of the renal fibrotic area percentage in the two groups at 4 and 8 weeks of age.

Hypoxanthine (HX) combined with potassium oxonate (PO) rapidly induces a hyperuricemia model with elevated serum uric acid and renal injury-related changes. This model is convenient, time-efficient, and suitable for early pharmacological evaluation of hyperuricemia and related renal complications.

(A) Serum uric acid levels in mice from different groups at the indicated time points; (B) urinary albumin-to-creatinine ratio (UACR) at the indicated time points. HX+PO treatment effectively elevated serum uric acid and was accompanied by renal injury-related changes. n=5-8 , Data presented as mean ± SD.

Following tamoxifen induction, conditional Uox-deficient mice developed a marked increase in serum uric acid, indicating successful establishment of a hyperuricemia-like phenotype. Treatment with allopurinol significantly reduced serum uric acid levels in the Uox-deficient mice, demonstrating good responsiveness to a classical urate-lowering agent and supporting the utility of this model for pharmacological and mechanistic studies of hyperuricemia.

(A) Serum uric acid levels in male mice at different time points.(B) Serum uric acid levels in female mice at different time points.Serum uric acid increased after tamoxifen induction and was reduced by allopurinol treatment. n=5, Data presented as mean ± SEM.