Construction method and applications of inducible transgenic mouse cardiomyopathy animal model

Abstract

The invention relates to an expression vector containing a calpain-1 gene. The expression vector comprises a Tet operon, an alpha-MHC promoter nucleotide sequence, a mitochondrial signal peptide sequence and a gene segment of calpain-1 which are connected in sequence. The invention further provides a construction method of an inducible transgenic mouse cardiomyopathy animal model. The constructionmethod comprises the following steps: importing the expression vector containing the calpain-1 gene into oosperms of a mouse, and transferring the oosperms into the uterus of the receptor mouse for gestation, thus obtaining the positive offspring transgenic mouse; and mating the positive offspring transgenic mouse with a transgenic mouse with specific expression of tTA or a transgenic mouse withspecific expression of rtTA, and picking out the inducible transgenic mouse cardiomyopathy animal model from the hybrid offsprings. The invention further discloses applications of the transgenic mousecardiomyopathy animal model obtained through the construction method in screening medicines for treating cardiomyopathy. According to the technical scheme provided by the invention, the modeling success rate is high, the phenotype is stable, the cost is ow, and whether inducting for the generation of cardiomyopathy is needed or not can be selected according to the actual demands.

Description

technical field [0001] The invention relates to the field of transgenic technology, in particular to a construction method and application of an inducible transgenic mouse cardiomyopathy animal model. Background technique [0002] Cardiomyopathy is a kind of myocardial disease caused by various reasons, characterized by myocardial enlargement, thickening and hardening. It is often manifested clinically as cardiac mechanical / electrical activity disturbance and abnormal hypertrophy or dilation of the ventricle. With the development of the disease, it can eventually evolve into heart failure. In recent years, the incidence of cardiomyopathy has been increasing year by year in the world, and it has become one of the most common clinical heart diseases in my country. The pathogenesis of cardiomyopathy is complex, the course of the disease is hidden, the prognosis is extremely poor, and there is a lack of specific treatment methods. It seriously endangers the health of the popula...

AI Technical Summary

Problems solved by technology

Disadvantages of this method: (1) The modeling time is too long, and it is reported in the literature that it takes more than one year at most; (2) There is a great potential risk in the use of the virus itself; (3) Myocarditis and The boundary of cardiomyopathy is not easy to accurately identify, and the feasibility is poor

Disadvantages of this method: (1) There is no uniform standard for the dosage of doxorubicin at present. Insufficient dosage may lead to modeling failure, while excessive dosage may lead to direct death; (2) intraperitoneal injection requires certain technical training. There is a certain failure rate due to the differences in the techniques of the operators

[0011] To sum up, there are obvious deficiencies in the current main cardiomyopathy animal models and modeling methods, and the current cardiomyopathy animal models cannot choose whether to induce cardiomyopathy according to actual needs.

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