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Method for constructing spontaneous hyperuricemia mouse model and application of mouse model

A hyperuricemia, mouse model technology, applied in the biological field, can solve problems such as inability to simulate human pathogenesis, gene functional inactivation, early termination of protein reading frames, etc., to achieve long-term experiments and long survival time. Effect

Inactive Publication Date: 2015-03-04
李长贵
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  • Abstract
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Problems solved by technology

However, the hyperuricemia mouse model reported in the literature has the following defects: (1) more than half of the homozygous mice with urate oxidase gene deletion died within 4 weeks after birth; (2) the blood uric acid level of the homozygous mice It is more than 10 times that of wild-type mice, and it is combined with fatal kidney disease, etc., so it cannot simulate the pathogenesis of humans
Artificially constructed sequence-specific endonucleases can recognize and cut specific DNA target sequences, causing double-strand breaks, resulting in premature translation termination or protein reading frame shift, and gene functional inactivation

Method used

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  • Method for constructing spontaneous hyperuricemia mouse model and application of mouse model
  • Method for constructing spontaneous hyperuricemia mouse model and application of mouse model
  • Method for constructing spontaneous hyperuricemia mouse model and application of mouse model

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Embodiment 1

[0047] Embodiment 1, the construction of spontaneous hyperuricemia mouse model

[0048] In this example, the urate oxidase gene of C57BL / 6J mice was knocked out by using the technique of transcription activator-like effector nuclease (TALEN), and the homozygous mice obtained by knocking out the urate oxidase gene were spontaneous hyperuricemia Hyperemia mouse model.

[0049] 1. TALEN site design

[0050] The mouse urate oxidase gene (MGI: 98907; gene chromosome location: Chr3: 146597077-146632305bp, +strand) can produce 4 transcripts, 2 of which can encode proteins. Urate oxidase-001, urate oxidase-003 were 303aa and 199aa, respectively. The inventors of the present invention designed a TALEN for the third exon of urate oxidase-001. The sequence information of this exon is as follows (the two target sequences of the designed TALEN are underlined, and the middle region is the spacer region of the TALEN) :

[0051] 5'-ATCAGAAACATCGAGACCT TTGCAATGAACATCT GTGAGCACTTCCTCTC ...

Embodiment 2

[0085] Embodiment 2, phenotype and physiological characteristic identification of F2 generation homozygous mice

[0086] 1. Observation of mouse phenotype

[0087] The F2 generation homozygous mice, heterozygous mice and littermate wild-type mice obtained in Example 1 were all similar to ordinary C57 mice. The coat color is black, the diet and activities are normal, and there is no hypoplasia or deformity. in Figure 8 It is a photo of the 8-week-old male homozygous mouse of the gene knockout obtained by TALEN technology in Example 1.

[0088] 2. Detection of blood uric acid level

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Abstract

The invention discloses a method for constructing a spontaneous hyperuricemia mouse model. The method for constructing the spontaneous hyperuricemia mouse model provided by the invention comprises the following step: knocking out urate oxidase genes of a target mouse by utilizing transcription activator-like effector nuclease to obtain a homozygote mouse from which the urate oxidase genes are knocked out, namely the spontaneous hyperuricemia mouse model. Experiments prove that the serum uric acid level of the spontaneous hyperuricemia mouse model obtained by the method disclosed by the invention is 3-4 times that of a wild type mouse and achieves the hyperuricemia level, and the pathogenesis of spontaneous hyperuricemia is better simulated. In addition, as the serum uric acid level of the mouse model obtained by the method disclosed by the invention is lower than the ultrahigh-level serum uric acid value reported in the previous literature, the lethal hyperuricemia does not exist, and the survival time of the mouse is long, so that long-term experiment of the mouse is facilitated.

Description

technical field [0001] The invention belongs to the field of biotechnology. A method relating to a model of spontaneous hyperuricemia mice and the use of the model. Background technique [0002] Hyperuricemia is a systemic disease caused by increased uric acid synthesis and / or decreased uric acid excretion. It has become a common metabolic disease, with a prevalence rate of 5%-23.5%, which is close to the level of developed countries in Europe and America. In recent years, research data at home and abroad have shown that 20% of patients with hyperuricemia can develop gout. In addition, as an independent risk factor for cardiovascular and cerebrovascular diseases, hyperuricemia can induce and aggravate atherosclerotic diseases, increase the morbidity and mortality of cardiovascular and cerebrovascular diseases, and at the same time, hyperuricemia is also associated with metabolic syndrome. , Kidney disease is closely related. [0003] Uric acid oxidase can decompose uric a...

Claims

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Application Information

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IPC IPC(8): C12N15/89A01K67/027
Inventor 李长贵路杰
Owner 李长贵
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