{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:26:59Z","timestamp":1789043219509,"version":"build-2803163510"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Our goal was to generate new rat strains for the study of human pathogenic viruses such as SARS-CoV-2 that use ACE2 for entry into host cells. An over-expression rat model was generated using random transgenesis to integrate copies of human\n                    <jats:italic>ACE2<\/jats:italic>\n                    under the control of the ubiquitously expressed CAG promoter into the rat genome. After transgene copy number, mRNA, and protein expression were confirmed, rats were challenged with the SARS-CoV-2 isolate USA-WA1\/2020. Wild type rats are not susceptible to high titer challenge, while rats hemizygous for the\n                    <jats:italic>ACE2<\/jats:italic>\n                    transgene lost significant body weight and displayed overt clinical signs of infection. This rat model will advance the understanding of COVID-19 and SARS-CoV-2 pathogenesis as well as accelerate the development of vaccines and antiviral therapies and can serve as an animal model for studies of the physiological role of ACE2.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2025.1680273","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:30:28Z","timestamp":1761719428000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Generation and characterization of a humanized ACE2 rat model for the study of SARS-CoV-2 and COVID-19"],"prefix":"10.3389","volume":"16","author":[{"given":"Rachel M.","family":"Olson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henda","family":"Nabli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina A.","family":"Gentry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig L.","family":"Franklin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary L.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C.","family":"Bryda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"535","DOI":"10.3390\/V14030535","article-title":"Fatal neurodissemination and SARS-CoV-2 tropism in K18-hACE2 mice is only partially dependent on hACE2 expression.","volume":"14","author":"Carossino","year":"2022","journal-title":"Viruses"},{"key":"B2","doi-asserted-by":"publisher","first-page":"4142","DOI":"10.3390\/molecules27134142","article-title":"K18-and CAG-hACE2 transgenic mouse models and SARS-CoV-2: Implications for neurodegeneration research.","volume":"27","author":"Dedoni","year":"2022","journal-title":"Molecules"},{"key":"B3","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1006\/VIRO.2000.0757","article-title":"Coronavirus spike proteins in viral entry and pathogenesis.","volume":"279","author":"Gallagher","year":"2001","journal-title":"Virology"},{"key":"B4","year":""},{"key":"B5","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/J.CELL.2020.09.050","article-title":"A mouse-adapted SARS-CoV-2 induces acute lung injury and mortality in standard laboratory mice.","volume":"183","author":"Leist","year":"2020","journal-title":"Cell"},{"key":"B6","doi-asserted-by":"publisher","first-page":"11429","DOI":"10.1128\/JVI.78.20.11429-11433.2004","article-title":"Efficient replication of severe acute respiratory syndrome coronavirus in mouse cells is limited by murine angiotensin-converting enzyme 2.","volume":"78","author":"Li","year":"2004","journal-title":"J. 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