A Mouse Model of SARS-CoV-2 Infection and Pathogenesis

Cell Host Microbe. 2020 Jul 8;28(1):124-133.e4. doi: 10.1016/j.chom.2020.05.020. Epub 2020 May 27.


Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought an urgent need for an animal model. Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis and evaluating COVID-19 vaccines and therapeutics.

Keywords: SARS-CoV-2; angiotensin-converting enzyme II; hACE2-KI/NIFDC; mouse model; pathogenesis.

MeSH terms

  • Aging
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Betacoronavirus / physiology*
  • Brain / virology
  • COVID-19
  • CRISPR-Cas Systems
  • Coronavirus Infections* / pathology
  • Coronavirus Infections* / virology
  • Cytokines / blood
  • Disease Models, Animal*
  • Gene Knock-In Techniques
  • Lung / pathology
  • Lung / virology
  • Lung Diseases, Interstitial / pathology
  • Mice, Inbred C57BL*
  • Nose / virology
  • Pandemics*
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral* / pathology
  • Pneumonia, Viral* / virology
  • RNA, Viral / analysis
  • SARS-CoV-2
  • Stomach / virology
  • Trachea / virology
  • Viral Load
  • Virus Replication


  • Cytokines
  • RNA, Viral
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2