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.

Uricase-Deficient Larval Zebrafish with Elevated Urate Levels Demonstrate Suppressed Acute Inflammatory Response to Monosodium Urate Crystals and Prolonged Crystal Persistence

“…An obstacle to using these uricase-deficient mice is their poor survival. Of note, A CRISPR/Cas9-generated uricase-deficient rat has also been generated that appears to have a more limited impact on survival [ 21 , 22 ].…”

Dieting alleviates hyperuricemia and organ injuries in uricase-deficient rats via down-regulating cell cycle pathway

“…As this study is follows on from our previous research, the materials used, and the procedures of animal housing, sample collection, biochemical assays, the abundance of genes expressed in organs, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis are similar to those reported previously ( Gao et al, 2022b ).…”

“…Uric acid is an end product of purine metabolism in humans, and uricase (urate oxidase, Uox) deficiency almost inhibits the conversion of uric acid to allantoin ( Jiang et al, 2021 ), a more soluble substance. Uric acid is directly transformed from xanthine by xanthine dehydrogenase (Xdh) and is excreted through urine and feces ( Gao et al, 2022b ). It is estimated that more than 80% of uric acid is synthesized from endogenous purines while less than 20% is obtained from the diet ( Basseville & Bates, 2011 ; Liu et al, 2019 ).…”

“…It is estimated that more than 80% of uric acid is synthesized from endogenous purines while less than 20% is obtained from the diet ( Basseville & Bates, 2011 ; Liu et al, 2019 ). Additionally, more than 80% of uric acid is excreted through urine, and less than 20% is excreted through feces ( Basseville & Bates, 2011 ; Gao et al, 2022b ). Elevated SUA levels can occur due to its increased synthesis or decreased excretion.…”

Efek Hepatoprotektor Ekstrak Etanol Kulit Melinjo terhadap Ekspresi Gen Alanine Aminotransferase 1 Hepar pada Kondisi Hiperurisemia

“…Sedangkan pada kelompok mamalia seperti mencit dan tikus memiliki rerata kadar asam urat yaitu hanya berkisar 1-2 mg/dl, pada tikus jantan galur wistar kadar asam urat normal yaitu 4,37±1,11 mg/dl (25,26).…”