Uricase-deficient rats with similarly stable serum uric acid to human's are sensitive model animals for studying hyperuricemia.

Abstract

The aim of this study was to provide a sensitive model animal for studying hyperuricemia. Male uricase-deficient rats, named Kunming-DY rats, were raised for 130 days, or orally administered with purines and other chemicals. Serum uric acid (SUA) in the animals was assayed, and the UA level in their organs and their 24-h excretion was determined. Genes in the jejunum, ileum, kidney and liver related to UA synthesis and transportation were detected by quantitative RNA sequencing. Uricase-deficient rats have a high level of SUA and are sensitive to xanthine, adenosine, inosine, allopurinol, and alcohol. Besides, the high level of SUA in male uricase-deficient rats was stable, much higher than that in wild-type rats but similar to that in men. The distribution pattern of UA in uricase-deficient rats' organs was different from that in wild-type rats. The kidney, liver, and small intestine were the top three organs where UA distributed, but the UA in the small intestine, colon, lung, thymus, and brain was less affected by uricase deficiency, indicating that these organs are constitutive distribution organs in UA. The 24-h UA excreted by a uricase-deficient rat was about five times higher than that excreted by a wild-type rat. However, the 24-h UA excreted through feces was not significantly changed. Both the urine volume and UA in uricase-deficient rats significantly increased, and more than 90% of UA was excreted via urine. The expression of xanthine dehydrogenase was not upregulated. Some genes of transporter associated with uric acid excretion in the kidney were significantly regulated, though not sufficient to explain the increase in SUA. In conclusion, male uricase-deficient rats' UA metabolism is similar to that of men. The elevation of SUA in uricase-deficient rats is caused by uricase deficiency, and uricase-deficient rats are a sensitive model for studying hyperuricemia.

• Authors: Yinfang Gao, Yun Yu, Wan Qin, Nan Fan, Yalin Qi, Huan Chen, Weigang Duan
• Journal: PloS one (PLoS One) Vol. 17 Issue 3 Pg. e0264696 ( 2022) ISSN: 1932-6203 [Electronic] United States
• PMID: 35239728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Uric Acid
• Allopurinol
• Urate Oxidase

Topics

• Allopurinol
• Animals
• Humans
• Hyperuricemia
• Kidney (metabolism)
• Male
• Rats
• Urate Oxidase (genetics, metabolism)
• Uric Acid