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Creation of transgenic mice susceptible to coronaviruses: a platform for studying viral pathogenesis and testing vaccines

Over the past 20 years, coronaviruses have caused three epidemics: SARS-CoV, MERS-CoV, and SARS-CoV2, with the f irst two having a very high lethality of about 10 and 26 %, respectively. The last outbreak of coronavirus infection caused by SARS-CoV2 in 2019 in China has swept the entire planet and i...

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Autores principales: Battulin, N.R., Serov, O.L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260647/
https://www.ncbi.nlm.nih.gov/pubmed/35864938
http://dx.doi.org/10.18699/VJGB-22-49
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author Battulin, N.R.
Serov, O.L.
author_facet Battulin, N.R.
Serov, O.L.
author_sort Battulin, N.R.
collection PubMed
description Over the past 20 years, coronaviruses have caused three epidemics: SARS-CoV, MERS-CoV, and SARS-CoV2, with the f irst two having a very high lethality of about 10 and 26 %, respectively. The last outbreak of coronavirus infection caused by SARS-CoV2 in 2019 in China has swept the entire planet and is still spreading. The source of these viruses in humans are animals: bats, Himalayan civets, and camels. The genomes of MERS-CoV, SARS-CoV and SARS-CoV2 are highly similar. It has been established that coronavirus infection (SARS-CoV and SARS-CoV2) occurs through the viral protein S interaction with the lung epithelium – angiotensin-converting enzyme receptor 2 (ACE2) – due to which the virus enters the cells. The most attractive model for studying the development of these diseases is a laboratory mouse, which, however, is resistant to coronavirus infection. The resistance is explained by the difference in the amino acid composition of mouse Ace2 and human ACE2 proteins. Therefore, to create mice susceptible to SARS- CoV and SARS-CoV2 coronaviruses, the human ACE2 gene is transferred into their genome. The exogenous DNA of the constructs is inserted into the recipient genome randomly and with a varying number of copies. Based on this technology, lines of transgenic mice susceptible to intranasal coronavirus infection have been created. In addition, the use of the technology of targeted genome modif ication using CRISPR/Cas9 made it possible to create lines of transgenic animals with the insertion of the human ACE2 gene under the control of the endogenous murine Ace2 gene promoter. This “humanization” of the Ace2 gene makes it possible to obtain animals susceptible to infection with coronaviruses. Thus, transgenic animals that simulate coronavirus infections and are potential platforms for testing vaccines have now been created
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spelling pubmed-92606472022-07-20 Creation of transgenic mice susceptible to coronaviruses: a platform for studying viral pathogenesis and testing vaccines Battulin, N.R. Serov, O.L. Vavilovskii Zhurnal Genet Selektsii Review Over the past 20 years, coronaviruses have caused three epidemics: SARS-CoV, MERS-CoV, and SARS-CoV2, with the f irst two having a very high lethality of about 10 and 26 %, respectively. The last outbreak of coronavirus infection caused by SARS-CoV2 in 2019 in China has swept the entire planet and is still spreading. The source of these viruses in humans are animals: bats, Himalayan civets, and camels. The genomes of MERS-CoV, SARS-CoV and SARS-CoV2 are highly similar. It has been established that coronavirus infection (SARS-CoV and SARS-CoV2) occurs through the viral protein S interaction with the lung epithelium – angiotensin-converting enzyme receptor 2 (ACE2) – due to which the virus enters the cells. The most attractive model for studying the development of these diseases is a laboratory mouse, which, however, is resistant to coronavirus infection. The resistance is explained by the difference in the amino acid composition of mouse Ace2 and human ACE2 proteins. Therefore, to create mice susceptible to SARS- CoV and SARS-CoV2 coronaviruses, the human ACE2 gene is transferred into their genome. The exogenous DNA of the constructs is inserted into the recipient genome randomly and with a varying number of copies. Based on this technology, lines of transgenic mice susceptible to intranasal coronavirus infection have been created. In addition, the use of the technology of targeted genome modif ication using CRISPR/Cas9 made it possible to create lines of transgenic animals with the insertion of the human ACE2 gene under the control of the endogenous murine Ace2 gene promoter. This “humanization” of the Ace2 gene makes it possible to obtain animals susceptible to infection with coronaviruses. Thus, transgenic animals that simulate coronavirus infections and are potential platforms for testing vaccines have now been created The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences 2022-07 /pmc/articles/PMC9260647/ /pubmed/35864938 http://dx.doi.org/10.18699/VJGB-22-49 Text en Copyright © AUTHORS https://creativecommons.org/licenses/by/2.5/This work is licensed under a Creative Commons Attribution 4.0 License
spellingShingle Review
Battulin, N.R.
Serov, O.L.
Creation of transgenic mice susceptible to coronaviruses: a platform for studying viral pathogenesis and testing vaccines
title Creation of transgenic mice susceptible to coronaviruses: a platform for studying viral pathogenesis and testing vaccines
title_full Creation of transgenic mice susceptible to coronaviruses: a platform for studying viral pathogenesis and testing vaccines
title_fullStr Creation of transgenic mice susceptible to coronaviruses: a platform for studying viral pathogenesis and testing vaccines
title_full_unstemmed Creation of transgenic mice susceptible to coronaviruses: a platform for studying viral pathogenesis and testing vaccines
title_short Creation of transgenic mice susceptible to coronaviruses: a platform for studying viral pathogenesis and testing vaccines
title_sort creation of transgenic mice susceptible to coronaviruses: a platform for studying viral pathogenesis and testing vaccines
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260647/
https://www.ncbi.nlm.nih.gov/pubmed/35864938
http://dx.doi.org/10.18699/VJGB-22-49
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