2022
DOI: 10.1128/jvi.00964-21
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The K18-Human ACE2 Transgenic Mouse Model Recapitulates Non-severe and Severe COVID-19 in Response to an Infectious Dose of the SARS-CoV-2 Virus

Abstract: The pandemic of coronavirus disease 2019 (COVID-19) has reached nearly 240 million cases, caused nearly 5 million deaths worldwide as of October 2021, and has raised an urgent need for the development of novel drugs and therapeutics to prevent the spread and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To achieve this goal, an animal model that recapitulates the features of human COVID-19 disease progress and pathogenesis is greatly needed.

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Cited by 128 publications
(124 citation statements)
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“…2,3). K18-hACE2 mice express human ACE2 driven by a cytokeratin promotor in epithelia, including airway epithelia cells where SARS-2 infections often start and recapitulate severe COVID-19 upon infection with SARS-2 (40)(41)(42). Viral challenges of K18-hACE2 mice result in extensive weight loss, and death usually results from SARS-2 or SARS-1 infection (41).…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…2,3). K18-hACE2 mice express human ACE2 driven by a cytokeratin promotor in epithelia, including airway epithelia cells where SARS-2 infections often start and recapitulate severe COVID-19 upon infection with SARS-2 (40)(41)(42). Viral challenges of K18-hACE2 mice result in extensive weight loss, and death usually results from SARS-2 or SARS-1 infection (41).…”
Section: Resultsmentioning
confidence: 99%
“…To compare the efficacies of mosaic and homotypic RBD-mi3 nanoparticle immunizations, we evaluated immune responses and protection from viral challenge in K18-human ACE2 (K18-hACE2) transgenic mice ( 40 ) (Fig. 2,3).…”
Section: Resultsmentioning
confidence: 99%
“…The K18-hACE2 transgenic model has been extensively utilized to evaluate the vaccine efficacy and effectiveness in preventing COVID-19 in the preclinical setting (Arce and Costoya, 2021; Dong et al, 2021; Radvak et al, 2021; Winkler et al, 2020). Two key metrics to determine the severity of pathogenesis are the virus titer in the lung tissue and body weight loss following virus infection.…”
Section: Resultsmentioning
confidence: 99%
“…A widely used mouse model of SARS-CoV-2 infection and COVID-19 disease is the K18-hACE2 mouse, where the human angiotensin-converting enzyme 2 (hACE2) is expressed as a transgene from the keratin 18 (K18) promoter. These mice develop a robust respiratory disease that histologically resembles severe COVID-19 (19)(20)(21). These mice have been widely used for evaluation of new interventions (22)(23)(24)(25)(26)(27), and for virology and immunopathology studies (28,29).…”
Section: Introductionmentioning
confidence: 99%