A tissue specific-infection mouse model of SARS-CoV-2
Abstract Animal models play crucial roles in the rapid development of vaccines/drugs for the prevention and therapy of COVID-19, but current models have some deficits when studying the pathogenesis of SARS-CoV-2 on some special tissues or organs. Here, we generated a human ACE2 and SARS-CoV-2 NF/F k...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-04-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-023-00536-0 |
| _version_ | 1797841203552583680 |
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| author | Bo Yang Chao Liu Xiaohui Ju Bingbing Wu Zhuangfei Wang Fucheng Dong Yanying Yu Xiaohui Hou Min Fang Fei Gao Xuejiang Guo Yaoting Gui Qiang Ding Wei Li |
| author_facet | Bo Yang Chao Liu Xiaohui Ju Bingbing Wu Zhuangfei Wang Fucheng Dong Yanying Yu Xiaohui Hou Min Fang Fei Gao Xuejiang Guo Yaoting Gui Qiang Ding Wei Li |
| author_sort | Bo Yang |
| collection | DOAJ |
| description | Abstract Animal models play crucial roles in the rapid development of vaccines/drugs for the prevention and therapy of COVID-19, but current models have some deficits when studying the pathogenesis of SARS-CoV-2 on some special tissues or organs. Here, we generated a human ACE2 and SARS-CoV-2 NF/F knockin mouse line that constitutively expresses human ACE2 and specifically expresses SARS-CoV-2 N gene induced by Cre-recombinase. By crossing with Cre transgenic lines allowing for lung-specific and constitutive expression, we generated lung-specific (Sftpc-hACE2-NF/F) and constitutive SARS-CoV-2 N (EIIa-hACE2-NF/F) expressing mice. Upon intranasal infection with a SARS-CoV-2 GFP/ΔN strain which can only replicate in SARS-CoV-2 N expressed cells, we demonstrated that both the Sftpc-hACE2-NF/F and EIIa-hACE2-NF/F mice support viral replication. Consistent with our design, viral replication was limited to the lung tissues in Sftpc-hACE2-NF/F mice, while the EIIa-hACE2-NF/F mice developed infections in multiple tissues. Furthermore, our model supports different SARS-CoV-2 variants infection, and it can be successfully used to evaluate the effects of therapeutic monoclonal antibodies (Ab1F11) and antiviral drugs (Molnupiravir). Finally, to test the effect of SARS-CoV-2 infection on male reproduction, we generated Sertoli cell-specific SARS-CoV-2 N expressed mice by crossing with AMH-Cre transgenic line. We found that SARS-CoV-2 GFP/ΔN strain could infect Sertoli cells, led to spermatogenic defects due to the destruction of blood-testis barrier. Overall, combining with different tissue-specific Cre transgenic lines, the human ACE2 and SARS-CoV-2 NF/F line enables us to evaluate antivirals in vivo and study the pathogenesis of SARS-CoV-2 on some special tissues or organs. |
| first_indexed | 2024-04-09T16:27:18Z |
| format | Article |
| id | doaj.art-42deab7eeb6a4211a0fcad54c773b244 |
| institution | Directory Open Access Journal |
| issn | 2056-5968 |
| language | English |
| last_indexed | 2024-04-09T16:27:18Z |
| publishDate | 2023-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj.art-42deab7eeb6a4211a0fcad54c773b2442023-04-23T11:09:12ZengNature Publishing GroupCell Discovery2056-59682023-04-019111610.1038/s41421-023-00536-0A tissue specific-infection mouse model of SARS-CoV-2Bo Yang0Chao Liu1Xiaohui Ju2Bingbing Wu3Zhuangfei Wang4Fucheng Dong5Yanying Yu6Xiaohui Hou7Min Fang8Fei Gao9Xuejiang Guo10Yaoting Gui11Qiang Ding12Wei Li13Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical CenterGuangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityCenter for Infectious Disease Research, School of Medicine, Tsinghua UniversityState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesGuangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesCenter for Infectious Disease Research, School of Medicine, Tsinghua UniversityZunyi Medical UniversityCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityGuangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical CenterCenter for Infectious Disease Research, School of Medicine, Tsinghua UniversityGuangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityAbstract Animal models play crucial roles in the rapid development of vaccines/drugs for the prevention and therapy of COVID-19, but current models have some deficits when studying the pathogenesis of SARS-CoV-2 on some special tissues or organs. Here, we generated a human ACE2 and SARS-CoV-2 NF/F knockin mouse line that constitutively expresses human ACE2 and specifically expresses SARS-CoV-2 N gene induced by Cre-recombinase. By crossing with Cre transgenic lines allowing for lung-specific and constitutive expression, we generated lung-specific (Sftpc-hACE2-NF/F) and constitutive SARS-CoV-2 N (EIIa-hACE2-NF/F) expressing mice. Upon intranasal infection with a SARS-CoV-2 GFP/ΔN strain which can only replicate in SARS-CoV-2 N expressed cells, we demonstrated that both the Sftpc-hACE2-NF/F and EIIa-hACE2-NF/F mice support viral replication. Consistent with our design, viral replication was limited to the lung tissues in Sftpc-hACE2-NF/F mice, while the EIIa-hACE2-NF/F mice developed infections in multiple tissues. Furthermore, our model supports different SARS-CoV-2 variants infection, and it can be successfully used to evaluate the effects of therapeutic monoclonal antibodies (Ab1F11) and antiviral drugs (Molnupiravir). Finally, to test the effect of SARS-CoV-2 infection on male reproduction, we generated Sertoli cell-specific SARS-CoV-2 N expressed mice by crossing with AMH-Cre transgenic line. We found that SARS-CoV-2 GFP/ΔN strain could infect Sertoli cells, led to spermatogenic defects due to the destruction of blood-testis barrier. Overall, combining with different tissue-specific Cre transgenic lines, the human ACE2 and SARS-CoV-2 NF/F line enables us to evaluate antivirals in vivo and study the pathogenesis of SARS-CoV-2 on some special tissues or organs.https://doi.org/10.1038/s41421-023-00536-0 |
| spellingShingle | Bo Yang Chao Liu Xiaohui Ju Bingbing Wu Zhuangfei Wang Fucheng Dong Yanying Yu Xiaohui Hou Min Fang Fei Gao Xuejiang Guo Yaoting Gui Qiang Ding Wei Li A tissue specific-infection mouse model of SARS-CoV-2 Cell Discovery |
| title | A tissue specific-infection mouse model of SARS-CoV-2 |
| title_full | A tissue specific-infection mouse model of SARS-CoV-2 |
| title_fullStr | A tissue specific-infection mouse model of SARS-CoV-2 |
| title_full_unstemmed | A tissue specific-infection mouse model of SARS-CoV-2 |
| title_short | A tissue specific-infection mouse model of SARS-CoV-2 |
| title_sort | tissue specific infection mouse model of sars cov 2 |
| url | https://doi.org/10.1038/s41421-023-00536-0 |
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