Hyperuricemia Models

Introduction

Urate is the end metabolite of purine compounds in humans, and purine metabolic disorders lead to hyperuricemia. The urate oxidase (UOX) gene encodes the enzyme uricase, which plays an important role in purine metabolism. Most mammals highly express UOX, but during human evolution, the UOX gene became silenced and inactivated, resulting in the production of uric acid as the end product of purine catabolism. When the rate of uric acid production exceeds the renal excretory capacity, serum uric acid levels rise significantly, thereby leading to hyperuricemia.

Disease models

Based on existing research, The SMOC has established a variety of mouse models related to hyperuricemia, providing powerful tools for in-depth investigation of the pathogenesis of hyperuricemia, drug screening, and evaluation of drug efficacy.

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Fig.1 Detection of mouse UOX expression in Uox-KO mice by WB. 

Abbr. M, marker; WT, wild type; HO, Homozygous.

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Fig.2 Body Weight of Uox-KO mouse. Values are expressed as mean ± SEM.

Abbr. WT, wild type.

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Fig.3 Uric acid (UA) levels of Uox-KO mouse (n=5-20). Values are expressed as mean ± SEM. 

Abbr. WT, wild type.

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Fig.4 The results of blood biochemical indicators of Uox-KO mouse (n=5-12). Values are expressed as mean ± SEM.

Abbr. WT, wild type.

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Fig.5 Observation of kidney and bladder. 

At 9 weeks of age, Uox-KO male mice had smaller kidneys with uneven surfaces compared to age-matched C57BL/6 mice. Some mice showed impaired urination, resulting in urine accumulation and bladder distention, which thinned the bladder wall.

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Fig.6 Histological analysis of kidney. 

16-week-old Uox-KO male mice revealed significant renal tubule atrophy (gray arrow), characterized by reduced volume and diminished eosinophilic cytoplasm. The interstitial space exhibited notable connective tissue proliferation (green arrow), accompanied by a substantial infiltration of lymphocytes (orange arrow) and macrophages (white arrow), with occasional necrotic cell debris (brown arrow). These features were absent in age-matched male WT mice. Scale bar=100 μm; magnification, 200×.

Abbr. WT, wild type 

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Fig.7 Effect of Allopurinol on Serum Uric Acid Levels. 12-16 week-old Uox-KO male mice were treated with Allopurinol. 

Compared to C57BL/6, serum uric acid levels of Uox-KO male mice were significantly elevated. Treatment with allopurinol (100mg/kg) significantly reduced serum uric acid levels in Uox-KO male mice (n=6-7). Values are expressed as mean ± SEM.

Abbr. WT, wild type.

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Fig.8 Kidney Function Assessment. Kidney function in Uox-KO male mice showed no significant difference compared to C57BL/6 mice (n=6-7). Values are expressed as mean ± SEM.

Abbr. WT, wild type 

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Fig.1 Body Weight of Uox-Flox/Alb-Cre mouse.

Abbr. WT, wild type.

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Fig.2 Uric acid (UA) levels of Uox-Flox/Alb-Cre mouse. 

Abbr. WT, wild type.

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Fig.3 The results of blood biochemical indicators of Uox-Flox/Alb-Cre mouse.

Abbr. WT, wild type.

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Fig.4 Histological analysis of kidney revealed no obvious micro-morphological injury in 20-week old Uox-Flox/Alb-Cre male mice.

Abbr. WT, wild type 

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Fig.5 Effect of Allopurinol on Serum Uric Acid Levels. 

6 week-old Uox-Flox/Alb-Cre male mice were treated with Allopurinol. Compared to C57BL/6, serum uric acid levels of Uox-Flox/Alb-Cre male mice were significantly elevated. Treatment with allopurinol (100mg/kg) significantly reduced serum uric acid levels in Uox-Flox/Alb-Cre male mice (n=10). Values are expressed as mean ± SEM.

Abbr. WT, wild type.

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Fig.6 Body Weight of Uox-Flox/Alb-Cre mouse.

The body weight of Uox-Flox/Alb-Cre male mice was lower compared to C57BL/6 mice. Allopurinol treatment had no effect on body weight (n=10). Values are expressed as mean ± SEM. 

Abbr. WT, wild type.

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Fig.7 Kidney Function Assessment of Uox-Flox/Alb-Cre mouse.

Kidney function in Uox-Flox/Alb-Cre male mice showed no significant difference compared to C57BL/6 mice (n=10). Values are expressed as mean ± SEM.

Abbr. WT, wild type 

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