Uox-KO(2)

Fig1. Construction of hyperuricemic model in Uox-ko mice. 

Uox-KO female mice were fed a synthetic diet containing allopurinol during pregnancy (Group 3), and the male offspring continued to be fed for 10 weeks after birth, with the levels of UA (uric acid), BUN (blood urea nitrogen), and body weight of the mice being measured.

Fig 2. Histological observation of kidney tissue in Uox-KO mice (HE & Masson staining). 

The results showed that the kidneys of Uox-KO mice exhibited interstitial fibrosis, inflammatory cell infiltration; glomerular atrophy, mesangial tissue proliferation; thickening of the vascular walls; dilation of renal tubules forming cysts; and homogeneous red-stained material exudation within the lumen of the renal tubules. Allopurinol (Group 3) was unable to ameliorate the kidney lesions caused by Uox-KO in mice. Uox-KO mice exhibit elevated uric acid levels and kidney damage similar to clinical conditions, and hyperuricemia treatment drugs can demonstrate the efficacy of lowering blood uric acid levels in these mice. Therefore, these mice can serve as a suitable model for the study of hyperuricemia and the evaluation of related drug effects.

Fig 3. Detection of mouse UOX expression in Uox-KO mice by WB. 

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

Fig 4. Body Weight of Uox-KO mouse. Values are expressed as mean ± SEM.

Abbr. WT, wild type.

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

Fig 6. The results of blood biochemical indicators of Uox-KO mouse (n=5-12). Values are expressed as mean ± SEM.

Fig 7. 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.

Fig 8. 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×.

Fig 9. 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.

Fig 10. 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.

Fig 11. survival curve of Uox-KO mice treated with allopurinol.