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However, wild\u2010type mice are not susceptible to COVID\u201019 infection due to the low affinity of mouse ACE2, the entry protein for SARS\u2010CoV\u20102. Although mice with human ACE2 (hACE2) driven by\n                    <jats:italic>Ace2<\/jats:italic>\n                    promoter reflect its tissue specificity, these animals exhibit low ACE2 expression, potentially limiting their fidelity in mimicking COVID\u201019 manifestations and their utility in viral studies. Here, we created and compared hACE2 mouse models generated with different strategies. Our findings show that distinct \u03b2\u2010globin insertion within hACE2 cassette significantly influences its expression, with downstream placement enhancing transcription. Moreover, optimizing hACE2 codons (opt\u2010hACE2) improves translation efficiency in multiple tissues. Notably, opt\u2010hACE2 mice displayed more active immune responses and severe COVID\u201019 phenotypes following SARS\u2010CoV\u20102 challenge compared to other models. Our study demonstrates the dual regulatory role of \u03b2\u2010globin element in transgene transcription and suggests that opt\u2010hACE2 mice might serve as valuable tools for SARS\u2010CoV\u20102 research.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.13934","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T01:55:05Z","timestamp":1735523705000},"page":"324-334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Enhancing human\n                    <scp>ACE2<\/scp>\n                    expression in mouse models to improve\n                    <scp>COVID<\/scp>\n                    \u201019 research"],"prefix":"10.1002","volume":"15","author":[{"given":"Sun","family":"Jiaoyang","sequence":"first","affiliation":[{"name":"Center for Cell Lineage and Development, Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences  Guangzhou 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