Background: Chronic hyperuricemia is associated with complications such as gout and uric acid nephropathy, but uric acid also exhibits biological activities (e.g., antioxidant effects, potential neuroprotective properties against neurodegenerative diseases). Nonhuman primates are ideal models for studying neurodegenerative diseases; however, existing nonhuman primate hyperuricemia models cannot sustain long-term elevated serum uric acid levels, nor recapitulate the impaired uric acid excretion observed in clinical hyperuricemic patients.
Methods: First, we detected uricase expression in cynomolgus monkeys and compared it with that in mice. Then, we established a cynomolgus monkey hyperuricemia model by administering a mixture of potassium oxonate, hydrochlorothiazide, and adenine via fruits and vegetables. We further analyzed the regulatory effects of this model on uric acid metabolism (synthesis, degradation, and excretion) and the expression of uric acid transporter genes in the intestine and kidney.
Results: Cynomolgus monkeys express functional uricase, but at a lower level than mice. The established model maintained stable, long-term hyperuricemia by three mechanisms: increasing intestinal and renal uric acid excretion load, inhibiting hepatic uric acid degradation, and promoting uric acid synthesis. Additionally, the model downregulated the expression of intestinal/renal uric acid-secreting transporter genes, while upregulating uric acid-reabsorbing transporter genes.
Conclusions: This novel cynomolgus monkey hyperuricemia model provides a new tool for investigating the association between hyperuricemia and neurodegenerative diseases, and will help clarify the mechanism by which serum uric acid influences cognitive function.
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2026 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.
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