A Mouse Model of SARS-CoV-2 Infection and Pathogenesis
Open accessAbstract
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.
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The ACE2 receptor is significantly different between mice and humans; so mouse models most often use a humanized ACE2 or lung passage to overcome this obstacle.
“Although mouse models have the most information available about their biology and many research tools, the ACE2 receptor is significantly different between mice and humans; so mouse models most often use a humanized ACE2 or lung passage to overcome this obstacle. 177-179”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [178]
The Introduction and Results (pages not provided) describe replacing mouse ACE2 with human ACE2 to create a SARS-CoV-2 mouse model, supporting humanization as one approach. The passages do not establish that the receptors are significantly different or that mouse models most often use either humanized ACE2 or lung passage; lung passage is not described. (LLM, conf=0.84)
Experimental — accuracy not yet measuredInvestigators found viral replication in a number of organs with the highest expression in the lung and brain and increased serum cytokines including IFNγ; however, the mouse background used in these models was C57BL/6, which responds to antigens with elevated Th1-type immune responses because they have few mast cells.
“Investigators found viral replication in a number of organs with the highest expression in the lung and brain and increased serum cytokines including IFN γ ; however, the mouse background used in these models was C57BL/6, which responds to antigens with elevated Th1-type immune responses because they have few mast cells. 160,177,178”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [178]
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- Authors
- Sun, S.-H., Chen, Q., Gu, H.-J., Yang, G., Wang, Y.-X., Huang, X.-Y., Liu, S.-S., Zhang, N.-N., Li, X.-F., Xiong, R., Guo, Y., Deng, Y.-Q., Huang, W.-J., Liu, Q., Liu, Q.-M., Shen, Y.-L., Zhou, Y., Yang, X., Zhao, T.-Y., Fan, C.-F., Zhou, Y.-S., Qin, C.-F., & Wang, Y.-C.
- Affiliations
- Academy of Military Medical Sciences (CN)
- Beijing Proteome Research Center (CN)
- National Institutes for Food and Drug Control (CN)
- Beijing Biocytogen (China) (CN)
- Corresponding author
- Zhou, Yu-Sen
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 28
- Issue
- 1
- Pages
- 124-133.e4
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC7250783
- OpenAlex
- W3031410383
- Cited by
- 617
- References
- 7
- Citations by year
- 2026: 19 · 2025: 31 · 2024: 68 · 2023: 82 · 2022: 138 · 2021: 178 · 2020: 101
- FWCI
- 16.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Research and Development Project (2016YFD0500304, 2020YFA0707801)
- National Science and Technology Major Project (2017ZX103304402, 2018ZX09711003)
- National Natural Science Foundation (82041006, 31871476)
- Guangdong Pearl River talent plan (2019CX01N111)
- National Science Fund for Distinguished Young Scholar (81925025)
- Innovative Research Group (81621005)
- the Innovation Fund for Medical Sciences (2019-I2M-5-049)
- Chinese Academy of Medical Sciences
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, mouse model, human ACE2, viral pathogenesis, viral load, interstitial lung disease, cytokines, aged mice, intragastric inoculation, intranasal infection, lung pathology, vaccine evaluation
- MeSH terms
- Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Aging, Animals, Brain, Disease Models, Animal, Peptidyl-Dipeptidase A, Lung, Mice, Inbred C57BL, Nose, Pneumonia, Viral, RNA, Viral, Stomach, Trachea, Virus Replication, Cytokines, Lung Diseases, Interstitial, Coronavirus Infections, Viral Load, Gene Knock-In Techniques, Pandemics, CRISPR-Cas Systems
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