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Construction method and application of DSC2 gene knockout mouse model

A gene knockout mouse and model technology, applied in application, genetic engineering, plant genetic improvement, etc., can solve the problems of different pathological mechanisms and treatment plans, many factors that interfere with the success of model induction, and cumbersome model building process.

Inactive Publication Date: 2021-09-21
ZHONGSHAN HOSPITAL FUDAN UNIV
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Problems solved by technology

Based on the current study of mouse models of right ventricular cardiomyopathy is relatively rare, and the mouse model of right heart failure usually adopts pulmonary artery coarctation or pulmonary embolism model, the process of constructing the model is cumbersome and there are many interference factors for the success of model induction
[0010] In the WHO classification of cardiomyopathy, some cardiomyopathy without significant arrhythmia is often attributed to arrhythmogenic right ventricular cardiomyopathy (ARVC), but in fact its pathological mechanism and treatment plan may be completely different. Due to the current ARVC mouse models have their own characteristics, but there are also many defects and problems, and there is no report on the right ventricular cardiomyopathy mouse model with simple right ventricular dilation and no arrhythmia

Method used

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  • Construction method and application of DSC2 gene knockout mouse model
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  • Construction method and application of DSC2 gene knockout mouse model

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Embodiment Construction

[0037] The invention provides a construction method and application of a DSC2 gene knockout mouse model.

[0038] Through wild-type mice (wt / wt), heterozygous mice (DSC2 - / - / wt) and homozygous mice (DSC2 - / - / DSC2 - / - ) three kinds of mice repeated experiments found that, with DSC2 - / - Compared with / wt heterozygous mice, DSC2 homozygous knockout mice can successfully induce the right ventricular cardiomyopathy model, while DSC2 heterozygote has no related manifestations such as heart enlargement, which further proves that only when DSC2 homozygous knockout Can effectively induce right ventricular cardiomyopathy.

[0039] Performance of DSC2 knockout mice in right ventricular cardiomyopathy: a systemic knockout of DSC2 was successfully constructed using CRISPR / Cas9 technology - / - For mice, from the age of 4 weeks, observe the mouse right ventricle (systolic area, long diameter, transverse diameter, basal segment; diastolic area, long diameter, transverse diameter, basal s...

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Abstract

The invention provides a construction method and application of a DSC2 gene knockout mouse model, and particularly relates to application of the DSC2 gene knockout mouse model in preparation of a reagent and a medicine for preventing and treating right heart disease, monitoring right ventricular diastole and contraction, and preparing an apoptosis pathway regulation reagent and a medicine or preparing a fibrosis pathway regulation reagent and a medicine. A DSC2 deletion mutant mouse is constructed on the basis of a C57BL / 6J mouse through a CRISPR-Cas9 technology, and the DSC2 knockout mouse can effectively induce right ventricular cardiomyopathy and can be used for a mouse model for right ventricular cardiomyopathy research; after the DSC2 gene is simply knocked out, along with the increase of the age of the mouse, the mouse has the expression of right ventricular cardiomyopathy such as right ventricular enlargement, right ventricular myocardial fibrosis and middle and advanced right ventricular heart failure, so that the mouse model can be used as an effective model in subsequent molecular mechanism research on the right ventricular cardiomyopathy.

Description

technical field [0001] The invention belongs to the technical field of bioengineering, and in particular relates to a construction method and application of a DSC2 gene knockout mouse model. Background technique [0002] Since Osler first described the disease mainly involving right ventricular muscle in 1905, parchment heart, Uhls malformation, right ventricular dysplasia and arrhythmia-derived right ventricular dysplasia have been reported successively. Since these diseases are mainly involved in the right ventricular myocardium, the etiology and mechanism of occurrence are unclear, Thiene collectively referred to them as right ventricular cardiomyopathy (RVC) in 1988. [0003] The clinical manifestations of right ventricular cardiomyopathy vary greatly. Some patients have no clinical manifestations and the heart is not enlarged, and are only discovered during autopsy or surgery. However, most patients may experience palpitations, fatigue, chest tightness, dizziness and sy...

Claims

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Application Information

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IPC IPC(8): A01K67/027C12N15/12
CPCA01K67/0276C07K14/70525A01K2217/075A01K2227/105A01K2267/0375Y02A50/30
Inventor 戴宇翔龚惠葛均波邹妍
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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