Novel transgenic mice with Cre-dependent co-expression of GFP and human ACE2: a safe tool for study of COVID-19 pathogenesis

Abstract Current coronavirus disease (COVID-19) pandemia still belongs to the most serious problems of public health. A growing body of data shows that infection caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a very complex and multifaceted disease requiring its detailed study to fight with. Nevertheless, there is a row of stumbling blocks in the way of experimental research of COVID-19 determined by the deficiency 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 the tissue-specific co-expression of hACE2 and GFP. Moreover, inducible expression of hACE2 makes this line biosafe, whereas co-expression 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, 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 role of different tissues in SARS-CoV-2 associated complications. Obviously, it can also be used for preclinical trials of antiviral drugs and new vaccines.