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Creation of a transgenic mouse model to study the SARS-CoV-2 effect on the pathogenesis of atherosclerosis

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Background and Aims: The novel coronavirus infection COVID-19 is claiming thousands of lives around the world. The impact of COVID-19 on CVD is actively studied by scientific community. It was… Click to show full abstract

Background and Aims: The novel coronavirus infection COVID-19 is claiming thousands of lives around the world. The impact of COVID-19 on CVD is actively studied by scientific community. It was found that COVID-19 affects not only the lungs, but also has a direct effect on cardiomyocytes, causes microvascular inflammation, including cytokine storm, and blood clotting disorders. To understand whether the SARS-CoV-2 virus makes a direct contribution to the damage to the circulatory system, we created a mouse model for the differential assessment of its pathogenesis in hypercholesterolemia. Methods: We used a genetic construct based on the Cre-LoxP system, due to which tissue-specific expression of the human ACE2 gene occurs. This gene encodes the Ace2 receptor that SARS-CoV-2 binds to when infected. After breeding mice with inducible human ACE2 gene super-expression with tissue-specific Cre-recomibinase expressing mice, we will get mice in which the ACE2 receptor will be produced only in certain body tissues, namely in endothelium, cardiomyocytes, macrophages. Results: A mouse strain for tissue-specific expression of human ACE2 gene was created. Conclusions: The model animals we have created with the expression of human ACE2 gene can be used in fundamental studies of the SARS-CoV-2 virus pathogenesis in various tissues against a background of hypercholesterolemia after breeding with ApoE-/- mice. This work was supported by the grant 075-15-2019-1661 from the Ministry of Science and Higher Education of the Russian Federation. The study was performed using the equipment of IGB RAS facilities supported by the Ministry of Science and Higher Education of the Russian Federation.

Keywords: human ace2; pathogenesis; sars cov; gene; mouse model

Journal Title: Atherosclerosis
Year Published: 2021

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