{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T22:34:38Z","timestamp":1784068478987,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82102369"],"award-info":[{"award-number":["82102369"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2016YFC1202905"],"award-info":[{"award-number":["2016YFC1202905"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Several animal models have been used to assist the development of vaccines and therapeutics since the COVID-19 outbreak. Due to the lack of binding affinity of mouse angiotensin-converting enzyme II (ACE2) to the S protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), increasing the susceptibility of mice to SARS-CoV-2 infection was considered in several ways. Here, we generated a COVID-19 mouse model expressing human ACE2 (hACE2) under the control of the CAG promoter. Overexpression of hACE2 did not pose a significant effect on weight growth. After SARS-CoV-2 inoculation, mice showed obvious viral replication and production of inflammation within 7\u2009days, with a gradual decrease in body weight until death. Virological testing found that the virus can replicate in the respiratory system, small intestine, and brain. Additionally, this mouse model was applied to compare two antibody drug candidates, the anti-RBD antibody (MW06) and the mouse CD24-conjugated anti-RBD antibody (mCD24-MW06). Differences in antiviral effects between these two antibodies can be demonstrated in this mouse model when a challenge dose that invalidates the anti-RBD antibody treatment was used. This study provided a new mouse model for studying SARS-CoV-2 pathogenesis and evaluating potential interventions.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1348405","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T19:39:19Z","timestamp":1707421159000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["A highly susceptible hACE2-transgenic mouse model for SARS-CoV-2 research"],"prefix":"10.3389","volume":"15","author":[{"given":"Gang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baolei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelian","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongjuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangwen","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehua","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhendong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yansong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/s41423-020-00616-1","article-title":"SARS-CoV-2 infection in K18-ACE2 transgenic mice replicates human pulmonary disease in COVID-19","volume":"18","author":"Arce","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e152529","DOI":"10.1172\/jci.insight.152529","article-title":"Highly susceptible SARS-CoV-2 model in CAG promoter-driven hACE2-transgenic mice","volume":"6","author":"Asaka","year":"2021","journal-title":"JCI Insight"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1038\/s41586-020-2312-y","article-title":"The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice","volume":"583","author":"Bao","year":"2020","journal-title":"Nature"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e1010867","DOI":"10.1371\/journal.ppat.1010867","article-title":"Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression","volume":"18","author":"Bishop","year":"2022","journal-title":"PLoS Pathog."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/s41392-022-00987-z","article-title":"Broadly neutralizing antibodies against omicron-included SARS-CoV-2 variants induced by vaccination","volume":"7","author":"Chi","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1177\/03009858221092015","article-title":"Animal models for studying COVID-19, prevention, and therapy: pathology and disease phenotypes","volume":"59","author":"Choudhary","year":"2022","journal-title":"Vet. Pathol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e0096421","DOI":"10.1128\/jvi.00964-21","article-title":"The K18-human ACE2 transgenic mouse model recapitulates non-severe and severe COVID-19 in response to an infectious dose of the SARS-CoV-2 virus","volume":"96","author":"Dong","year":"2022","journal-title":"J. Virol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/s41392-022-01087-8","article-title":"Animal models for COVID-19: advances, gaps and perspectives","volume":"7","author":"Fan","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"11","DOI":"10.7554\/eLife.74623","article-title":"ACE2 is the critical in vivo receptor for SARS-CoV-2 in a novel COVID-19 mouse model with TNF- and IFN\u03b3-driven immunopathology","volume":"11","author":"Gawish","year":"2022","journal-title":"elife"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e142032","DOI":"10.1172\/jci.insight.142032","article-title":"Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease","volume":"5","author":"Golden","year":"2020","journal-title":"JCI Insight"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e0290621","DOI":"10.1128\/mbio.02906-21","article-title":"Hamsters expressing human angiotensin-converting enzyme 2 develop severe disease following exposure to SARS-CoV-2","volume":"13","author":"Golden","year":"2022","journal-title":"MBio"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1126\/science.abc4730","article-title":"Adaptation of SARS-CoV-2 in BALB\/c mice for testing vaccine efficacy","volume":"369","author":"Gu","year":"2020","journal-title":"Science"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1002\/path.1570","article-title":"Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. 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Pathol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.cell.2020.05.027","article-title":"Pathogenesis of SARS-CoV-2 in transgenic mice expressing human angiotensin-converting enzyme 2","volume":"182","author":"Jiang","year":"2020","journal-title":"Cell"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1953683","DOI":"10.1080\/19420862.2021.1953683","article-title":"Characterization of MW06, a human monoclonal antibody with cross-neutralization activity against both SARS-CoV-2 and SARS-CoV","volume":"13","author":"Jiang","year":"2021","journal-title":"MAbs"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1038\/s41385-020-00340-z","article-title":"Animal and translational models of SARS-CoV-2 infection and COVID-19","volume":"13","author":"Johansen","year":"2020","journal-title":"Mucosal Immunol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"383","DOI":"10.30802\/aalas-cm-21-000031","article-title":"Mouse models for the study of SARS-CoV-2 infection","volume":"71","author":"Knight","year":"2021","journal-title":"Comp. 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Hyg."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/s41586-020-2787-6","article-title":"Animal models for COVID-19","volume":"586","author":"Mu\u00f1oz-Fontela","year":"2020","journal-title":"Nature"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e1010161","DOI":"10.1371\/journal.ppat.1010161","article-title":"Advances and gaps in SARS-CoV-2 infection models","volume":"18","author":"Mu\u00f1oz-Fontela","year":"2022","journal-title":"PLoS Pathog."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1007\/s11427-018-9343-8","article-title":"A novel human mAb (MERS-GD27) provides prophylactic and postexposure efficacy in MERS-CoV susceptible mice","volume":"61","author":"Niu","year":"2018","journal-title":"Sci. China Life Sci."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"6122","DOI":"10.1038\/s41467-020-19891-7","article-title":"Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice","volume":"11","author":"Oladunni","year":"2020","journal-title":"Nat. Commun."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1002\/ame2.12278","article-title":"Characteristics of animal models for COVID-19","volume":"5","author":"Qi","year":"2022","journal-title":"Anim. Model Exp. Med."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"85","DOI":"10.5501\/wjv.v5.i2.85","article-title":"Determination of 50% endpoint titer using a simple formula","volume":"5","author":"Ramakrishnan","year":"2016","journal-title":"World J. Virol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1080\/22221751.2020.1838955","article-title":"Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection","volume":"9","author":"Rathnasinghe","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"107931","DOI":"10.1016\/j.pharmthera.2021.107931","article-title":"Animal models of SARS-CoV-2 and COVID-19 for the development of prophylactic and therapeutic interventions","volume":"228","author":"Renn","year":"2021","journal-title":"Pharmacol. 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Oncol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.chom.2020.05.020","article-title":"A mouse model of SARS-CoV-2 infection and pathogenesis","volume":"28","author":"Sun","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1128\/jvi.01702-06","article-title":"Severe acute respiratory syndrome coronavirus infection of mice transgenic for the human angiotensin-converting enzyme 2 virus receptor","volume":"81","author":"Tseng","year":"2007","journal-title":"J. Virol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"331","DOI":"10.30802\/aalas-cm-21-000090","article-title":"COVID-19 and animal-based research","volume":"71","author":"Villano","year":"2021","journal-title":"Comp. 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Comparative virology and disease pathogenesis","volume":"62","author":"Zeiss","year":"2021","journal-title":"ILAR J."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1080\/21645515.2015.1103405","article-title":"Generation of human MHC (HLA-A11\/DR1) transgenic mice for vaccine evaluation","volume":"12","author":"Zeng","year":"2016","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"907406","DOI":"10.3389\/fmicb.2022.907406","article-title":"Animal models for COVID-19 therapeutic development: where we are and where we need to go","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Microbiol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1348405\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T19:39:23Z","timestamp":1707421163000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1348405\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,7]]},"references-count":41,"alternative-id":["10.3389\/fmicb.2024.1348405"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2024.1348405","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,7]]},"article-number":"1348405"}}