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

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PLoS One


. 2022 Jul 26;17(7):e0272019.
doi: 10.1371/journal.pone.0272019. eCollection 2022.
Development of transgenic models susceptible and resistant to SARS-CoV-2 infection in FVB background mice


Sun-Min Seo ¹ , Jae Hyung Son ² , Ji-Hun Lee ¹ , Na-Won Kim ¹ , Eun-Seon Yoo ¹ , Ah-Reum Kang ¹ , Ji Yun Jang ^{2 3} , Da In On ⁴ , Hyun Ah Noh ⁴ , Jun-Won Yun ^{5 6} , Jun Won Park ⁷ , Kang-Seuk Choi ⁸ , Ho-Young Lee ⁹ , Jeon-Soo Shin ¹⁰ , Jun-Young Seo ¹¹ , Ki Taek Nam ¹¹ , Ho Lee ² , Je Kyung Seong ¹² , Yang-Kyu Choi ¹



Affiliations

• PMID: 35881617
• DOI: 10.1371/journal.pone.0272019

Abstract

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.