tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Jae Hyung Son[SUP] 2 [/SUP], Ji-Hun Lee[SUP] 1 [/SUP], Na-Won Kim[SUP] 1 [/SUP], Eun-Seon Yoo[SUP] 1 [/SUP], Ah-Reum Kang[SUP] 1 [/SUP], Ji Yun Jang[SUP] 2 3 [/SUP], Da In On[SUP] 4 [/SUP], Hyun Ah Noh[SUP] 4 [/SUP], Jun-Won Yun[SUP] 5 6 [/SUP], Jun Won Park[SUP] 7 [/SUP], Kang-Seuk Choi[SUP] 8 [/SUP], Ho-Young Lee[SUP] 9 [/SUP], Jeon-Soo Shin[SUP] 10 [/SUP], Jun-Young Seo[SUP] 11 [/SUP], Ki Taek Nam[SUP] 11 [/SUP], Ho Lee[SUP] 2 [/SUP], Je Kyung Seong[SUP] 12 [/SUP], Yang-Kyu Choi[SUP] 1 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], Jae Hyung Son[SUP] 2 [/SUP], Ji-Hun Lee[SUP] 1 [/SUP], Na-Won Kim[SUP] 1 [/SUP], Eun-Seon Yoo[SUP] 1 [/SUP], Ah-Reum Kang[SUP] 1 [/SUP], Ji Yun Jang[SUP] 2 3 [/SUP], Da In On[SUP] 4 [/SUP], Hyun Ah Noh[SUP] 4 [/SUP], Jun-Won Yun[SUP] 5 6 [/SUP], Jun Won Park[SUP] 7 [/SUP], Kang-Seuk Choi[SUP] 8 [/SUP], Ho-Young Lee[SUP] 9 [/SUP], Jeon-Soo Shin[SUP] 10 [/SUP], Jun-Young Seo[SUP] 11 [/SUP], Ki Taek Nam[SUP] 11 [/SUP], Ho Lee[SUP] 2 [/SUP], Je Kyung Seong[SUP] 12 [/SUP], Yang-Kyu Choi[SUP] 1 [/SUP]
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.