Uox KO Mice

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Product Number：C001232

Genetic Background：C57BL/6JCya

Reproduction：Homozygote x Homozygote


Strain Description

Uricase, which is encoded by the urate oxidase (UOX) gene, has an important role in the purine metabolic pathway, and most mammals contain UOX, which breaks down uric acid, a metabolite of purine nucleotides, into allantoin, which is more soluble than uric acid. Unlike other mammals, humans lack UOX, and purine catabolism can only produce uric acid, which is subsequently excreted by the kidneys, resulting in higher serum uric acid concentrations in humans than in other mammals. When the rate of uric acid production exceeds the excretory capacity of the kidneys, the serum uric acid level increases significantly, resulting in hyperuricemia.UOX can significantly reduce plasma uric acid levels and can treat gout and kidney disease secondary to hyperuricemia, among others[1]. This strain is a Uox gene deletion mouse, in which the synthesis of uricase is blocked in the mouse organism and the hyperuricemia phenotype occurs spontaneously. The heterozygous Uox KO mice are viable and fertile.

 

The Uox gene is located on mouse chromosome 3, and Exon 3~4 of this gene was deleted by gene editing techniques.

The Uox KO mice can be used in the study of hyperuricemia, gout, and its related kidney disease.

Approximately 65% of homozygous Uox KO mice die successively after a few weeks of life and therefore need to be maintained after birth with drugs such as allopurinol[2].

1. The growth curve

Figure 1. The growth curve of homozygous Uox-/- mice. The mice were grouped and given different concentrations of allopurinol, and their body weight was measured weekly. The results showed that the trend of body weight change was similar in all groups from 3-8 weeks with no significant difference; at 9-10W, the body weight of mice in the G3 group decreased and then remained unchanged.
(G1: Uox-/- mice + normal drinking, G2: Uox-/- mice + low dose allopurinol drinking, G3: Uox-/- mice + medium dose allopurinol drinking, G4: Uox-/- mice + high dose allopurinol drinking, G5: WT mice + normal drinking, Same below)

2. The survival curve

Figure 2. The survival curve of homozygous Uox-/- mice. Mice were grouped and given different concentrations of allopurinol, and survival status was monitored weekly. The results showed that the survival rate of Uox-/- mice in the G2 low-dose allopurinol group was always at 100%, while the survival rate of the other three groups started to decrease at 4 weeks. At the 10 weeks, the survival rates of the G1, G3, and G4 groups were 75%, 25%, and 25%, respectively.

3. Blood biochemical indices

Figure 3. The blood biochemical parameters of homozygous Uox-/- mice. The results showed that compared with wild-type mice in the G5 control group, Uox-/- mice in the G1 group showed hyperuricemia characterized by elevated levels of urea nitrogen (BUN), creatinine (CREA), and uric acid (UA) at 6 weeks and 8 weeks. Uox-/- mice fed allopurinol showed elevated levels of urea nitrogen, creatinine, and uric acid with increasing feeding concentrations, and elevation was more pronounced in female mice than in male mice.

 

The mice were fed with drinking water with 100 mg/L of allopurinol during both the gestation period of the mothers and the foster period of the offspring until the offspring were separated.

 

References

[1] Lu J , Dalbeth N, Yin H , et al. Mouse models for human hyperuricaemia: a critical review[J]. Nature Reviews Rheumatology, 2019, 15(Suppl. 10):1.
[2] Wu X . Hyperuricemia and urate nephropathy in urate oxidase-deficient mice[J]. Proc Natl Acad Sci U S A, 1994, 91.