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Development of transgenic models susceptible and resistant to SARS-CoV-2 infection in FVB background mice

 Sun-Min Seo  ;  Jae Hyung Son  ;  Ji-Hun Lee  ;  Na-Won Kim  ;  Eun-Seon Yoo  ;  Ah-Reum Kang  ;  Ji Yun Jang  ;  Da In On  ;  Hyun Ah Noh  ;  Jun-Won Yun  ;  Jun Won Park  ;  Kang-Seuk Choi  ;  Ho-Young Lee  ;  Jeon-Soo Shin  ;  Jun-Young Seo  ;  Ki Taek Nam  ;  Ho Lee  ;  Je Kyung Seong  ;  Yang-Kyu Choi 
 PLOS ONE, Vol.17(7) : e0272019, 2022-07 
Journal Title
Issue Date
Angiotensin-Converting Enzyme 2 / genetics ; Animals ; Atrophy / pathology ; COVID-19* ; Disease Models, Animal ; Disease Susceptibility / pathology ; Humans ; Lung / pathology ; Mice ; Mice, Inbred Strains ; Mice, Transgenic ; Pandemics ; Peptidyl-Dipeptidase A ; Pneumonia* / pathology ; SARS-CoV-2
Coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is currently spreading globally. To overcome the COVID-19 pandemic, preclinical evaluations of vaccines and therapeutics using K18-hACE2 and CAG-hACE2 transgenic mice are ongoing. However, a comparative study on SARS-CoV-2 infection between K18-hACE2 and CAG-hACE2 mice has not been published. In this study, we compared the susceptibility and resistance to SARS-CoV-2 infection between two strains of transgenic mice, which were generated in FVB background mice. K18-hACE2 mice exhibited severe weight loss with definitive lethality, but CAG-hACE2 mice survived; and differences were observed in the lung, spleen, cerebrum, cerebellum, and small intestine. A higher viral titer was detected in the lungs, cerebrums, and cerebellums of K18-hACE2 mice than in the lungs of CAG-hACE2 mice. Severe pneumonia was observed in histopathological findings in K18-hACE2, and mild pneumonia was observed in CAG-hACE2. Atrophy of the splenic white pulp and reduction of spleen weight was observed, and hyperplasia of goblet cells with villi atrophy of the small intestine was observed in K18-hACE2 mice compared to CAG-hACE2 mice. These results indicate that K18-hACE2 mice are relatively susceptible to SARS-CoV-2 and that CAG-hACE2 mice are resistant to SARS-CoV-2. Based on these lineage-specific sensitivities, we suggest that K18-hACE2 mouse is suitable for highly susceptible model of SARS-CoV-2, and CAG-hACE2 mouse is suitable for mild susceptible model of SARS-CoV-2 infection.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Nam, Ki Taek(남기택)
Seo, Jun Young(서준영) ORCID logo https://orcid.org/0000-0003-4004-2013
Shin, Jeon Soo(신전수) ORCID logo https://orcid.org/0000-0002-8294-3234
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