高尿酸血症疾病模型

疾病简介

尿酸(urate)是人类嘌呤化合物的终末代谢产物,嘌呤代谢紊乱导致高尿酸血症。尿酸氧化酶(urate oxidase, UOX)基因编码的尿酸酶(Uricase)在嘌呤的代谢过程中起重要作用,多数哺乳类动物体内高表达UOX,人类在进化过程中,体内的Uox基因沉默失活,因此嘌呤分解代谢只能生成尿酸。当尿酸生成速度超过肾脏的排泄能力时,血清的尿酸水平会显著升高,进而引发高尿酸血症。

疾病模型

基于现有研究,南模生物建立了多种高尿酸血症相关小鼠模型,为深入探究高尿酸血症的发病机理、进行药物筛选以及评估药物疗效提供了强有力的工具。

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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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