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Novel transgenic mice with Cre-dependent co-expression of GFP and human ACE2: a safe tool for study of COVID-19 pathogenesis
The current coronavirus disease (COVID-19) pandemic remains one of the most serious public health problems. Increasing evidence shows that infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a very complex and multifaceted disease that requires detailed study. Neverthele...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045570/ https://www.ncbi.nlm.nih.gov/pubmed/33855640 http://dx.doi.org/10.1007/s11248-021-00249-8 |
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author | Bruter, Alexandra V. Korshunova, Diana S. Kubekina, Marina V. Sergiev, Petr V. Kalinina, Anastasiia A. Ilchuk, Leonid A. Silaeva, Yuliya Yu. Korshunov, Eugenii N. Soldatov, Vladislav O. Deykin, Alexey V. |
author_facet | Bruter, Alexandra V. Korshunova, Diana S. Kubekina, Marina V. Sergiev, Petr V. Kalinina, Anastasiia A. Ilchuk, Leonid A. Silaeva, Yuliya Yu. Korshunov, Eugenii N. Soldatov, Vladislav O. Deykin, Alexey V. |
author_sort | Bruter, Alexandra V. |
collection | PubMed |
description | The current coronavirus disease (COVID-19) pandemic remains one of the most serious public health problems. Increasing evidence shows that infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a very complex and multifaceted disease that requires detailed study. Nevertheless, experimental research on COVID-19 remains challenging due to the lack of appropriate animal models. Herein, we report novel humanized mice with Cre-dependent expression of hACE2, the main entry receptor of SARS-CoV-2. These mice carry hACE2 and GFP transgenes floxed by the STOP cassette, allowing them to be used as breeders for the creation of animals with tissue-specific coexpression of hACE2 and GFP. Moreover, inducible expression of hACE2 makes this line biosafe, whereas coexpression with GFP simplifies the detection of transgene-expressing cells. In our study, we tested our line by crossing with Ubi-Cre mice, characterized by tamoxifen-dependent ubiquitous activation of Cre recombinase. After tamoxifen administration, the copy number of the STOP cassette was decreased, and the offspring expressed hACE2 and GFP, confirming the efficiency of our system. We believe that our model can be a useful tool for studying COVID-19 pathogenesis because the selective expression of hACE2 can shed light on the roles of different tissues in SARS-CoV-2-associated complications. Obviously, it can also be used for preclinical trials of antiviral drugs and new vaccines. GRAPHIC ABSTRACT: [Image: see text] |
format | Online Article Text |
id | pubmed-8045570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-80455702021-04-15 Novel transgenic mice with Cre-dependent co-expression of GFP and human ACE2: a safe tool for study of COVID-19 pathogenesis Bruter, Alexandra V. Korshunova, Diana S. Kubekina, Marina V. Sergiev, Petr V. Kalinina, Anastasiia A. Ilchuk, Leonid A. Silaeva, Yuliya Yu. Korshunov, Eugenii N. Soldatov, Vladislav O. Deykin, Alexey V. Transgenic Res Original Paper The current coronavirus disease (COVID-19) pandemic remains one of the most serious public health problems. Increasing evidence shows that infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a very complex and multifaceted disease that requires detailed study. Nevertheless, experimental research on COVID-19 remains challenging due to the lack of appropriate animal models. Herein, we report novel humanized mice with Cre-dependent expression of hACE2, the main entry receptor of SARS-CoV-2. These mice carry hACE2 and GFP transgenes floxed by the STOP cassette, allowing them to be used as breeders for the creation of animals with tissue-specific coexpression of hACE2 and GFP. Moreover, inducible expression of hACE2 makes this line biosafe, whereas coexpression with GFP simplifies the detection of transgene-expressing cells. In our study, we tested our line by crossing with Ubi-Cre mice, characterized by tamoxifen-dependent ubiquitous activation of Cre recombinase. After tamoxifen administration, the copy number of the STOP cassette was decreased, and the offspring expressed hACE2 and GFP, confirming the efficiency of our system. We believe that our model can be a useful tool for studying COVID-19 pathogenesis because the selective expression of hACE2 can shed light on the roles of different tissues in SARS-CoV-2-associated complications. Obviously, it can also be used for preclinical trials of antiviral drugs and new vaccines. GRAPHIC ABSTRACT: [Image: see text] Springer International Publishing 2021-04-14 2021 /pmc/articles/PMC8045570/ /pubmed/33855640 http://dx.doi.org/10.1007/s11248-021-00249-8 Text en © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Original Paper Bruter, Alexandra V. Korshunova, Diana S. Kubekina, Marina V. Sergiev, Petr V. Kalinina, Anastasiia A. Ilchuk, Leonid A. Silaeva, Yuliya Yu. Korshunov, Eugenii N. Soldatov, Vladislav O. Deykin, Alexey V. Novel transgenic mice with Cre-dependent co-expression of GFP and human ACE2: a safe tool for study of COVID-19 pathogenesis |
title | Novel transgenic mice with Cre-dependent co-expression of GFP and human ACE2: a safe tool for study of COVID-19 pathogenesis |
title_full | Novel transgenic mice with Cre-dependent co-expression of GFP and human ACE2: a safe tool for study of COVID-19 pathogenesis |
title_fullStr | Novel transgenic mice with Cre-dependent co-expression of GFP and human ACE2: a safe tool for study of COVID-19 pathogenesis |
title_full_unstemmed | Novel transgenic mice with Cre-dependent co-expression of GFP and human ACE2: a safe tool for study of COVID-19 pathogenesis |
title_short | Novel transgenic mice with Cre-dependent co-expression of GFP and human ACE2: a safe tool for study of COVID-19 pathogenesis |
title_sort | novel transgenic mice with cre-dependent co-expression of gfp and human ace2: a safe tool for study of covid-19 pathogenesis |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045570/ https://www.ncbi.nlm.nih.gov/pubmed/33855640 http://dx.doi.org/10.1007/s11248-021-00249-8 |
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