Journal Article

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

Son, Jae Hyung, On, Da In, Lee, Ho-Young, Shin, Jeon-Soo, Seo, Sun-Min, Noh, Hyun Ah, Yoo, Eun-Seon, Jang, Ji Yun, Nam, Ki Taek, Choi, Yang-Kyu, Lee, Ji-Hun, Yun, Jun-Won, Lee, Ho, Choi, Kang-Seuk, Kang, Ah-Reum, Kim, Na-Won, Seo, Jun-Young, Park, Jun Won, Seong, Je Kyung

2022

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Angiotensin-Converting Enzyme 2 - genetics / Animals / Atrophy / Atrophy - pathology / Biology and life sciences / Cerebellum / Cerebrum / Comparative studies / Coronaviruses / COVID-19 / Disease Models, Animal / Disease susceptibility / Disease Susceptibility - pathology / Engineering and Technology / Genetic engineering / Genetically modified mice / Goblet cells / Humans / Hyperplasia / Infections / Intestine / Laboratories / Lethality / Lung - pathology / Lungs / Medical research / Medicine and health sciences / Medicine, Experimental / Methods / Mice / Mice, Inbred Strains / Mice, Transgenic / Pandemics / Peptidyl-Dipeptidase A / Pneumonia / Pneumonia - pathology / Research and Analysis Methods / Respiratory diseases / Rodents / SARS-CoV-2 / Severe acute respiratory syndrome / Severe acute respiratory syndrome coronavirus 2 / Small intestine / Spleen / Transgenic mice / Trinucleotide repeats / Vaccines / Viral diseases / Weight loss / White pulp