Enhancing human ACE2 expression in mouse models to improve COVID‐19 research
Mice are one of the most common biological models for laboratory use. However, wild‐type mice are not susceptible to COVID‐19 infection due to the low affinity of mouse ACE2, the entry protein for SARS‐CoV‐2. Although mice with human ACE2 (hACE2) driven by Ace2 promoter reflect its tissue specificit...
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| Format: | Article |
| Language: | English |
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Wiley
2025-02-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.13934 |
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| _version_ | 1832544049710497792 |
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| author | Sun Jiaoyang Cheng Shaofei Hong Guangliang Quan Xiongzhi Lin Haofeng Mao Rui Johannes Grillari Shi Zheng‐Li Chen Jiekai Liu Meiqin Wu Haoyu Wu Guangming |
| author_facet | Sun Jiaoyang Cheng Shaofei Hong Guangliang Quan Xiongzhi Lin Haofeng Mao Rui Johannes Grillari Shi Zheng‐Li Chen Jiekai Liu Meiqin Wu Haoyu Wu Guangming |
| author_sort | Sun Jiaoyang |
| collection | DOAJ |
| description | Mice are one of the most common biological models for laboratory use. However, wild‐type mice are not susceptible to COVID‐19 infection due to the low affinity of mouse ACE2, the entry protein for SARS‐CoV‐2. Although mice with human ACE2 (hACE2) driven by Ace2 promoter reflect its tissue specificity, these animals exhibit low ACE2 expression, potentially limiting their fidelity in mimicking COVID‐19 manifestations and their utility in viral studies. Here, we created and compared hACE2 mouse models generated with different strategies. Our findings show that distinct β‐globin insertion within hACE2 cassette significantly influences its expression, with downstream placement enhancing transcription. Moreover, optimizing hACE2 codons (opt‐hACE2) improves translation efficiency in multiple tissues. Notably, opt‐hACE2 mice displayed more active immune responses and severe COVID‐19 phenotypes following SARS‐CoV‐2 challenge compared to other models. Our study demonstrates the dual regulatory role of β‐globin element in transgene transcription and suggests that opt‐hACE2 mice might serve as valuable tools for SARS‐CoV‐2 research. |
| format | Article |
| id | doaj-art-3f2ce17b104c4a008a17d653d9e63c57 |
| institution | Kabale University |
| issn | 2211-5463 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj-art-3f2ce17b104c4a008a17d653d9e63c572025-02-03T10:59:30ZengWileyFEBS Open Bio2211-54632025-02-0115232433410.1002/2211-5463.13934Enhancing human ACE2 expression in mouse models to improve COVID‐19 researchSun Jiaoyang0Cheng Shaofei1Hong Guangliang2Quan Xiongzhi3Lin Haofeng4Mao Rui5Johannes Grillari6Shi Zheng‐Li7Chen Jiekai8Liu Meiqin9Wu Haoyu10Wu Guangming11Center for Cell Lineage and Development, Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou ChinaCenter for Cell Lineage and Development, Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou ChinaGuangzhou National Laboratory Guangzhou ChinaCenter for Cell Lineage and Development, Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou ChinaWuhan Institute of Virology Chinese Academy of Sciences Wuhan ChinaLaboratory Animal Research Centre, Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou ChinaAustrian Cluster for Tissue Regeneration Vienna AustriaGuangzhou National Laboratory Guangzhou ChinaCenter for Cell Lineage and Development, Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou ChinaWuhan Institute of Virology Chinese Academy of Sciences Wuhan ChinaCenter for Cell Lineage and Development, Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou ChinaGuangzhou National Laboratory Guangzhou ChinaMice are one of the most common biological models for laboratory use. However, wild‐type mice are not susceptible to COVID‐19 infection due to the low affinity of mouse ACE2, the entry protein for SARS‐CoV‐2. Although mice with human ACE2 (hACE2) driven by Ace2 promoter reflect its tissue specificity, these animals exhibit low ACE2 expression, potentially limiting their fidelity in mimicking COVID‐19 manifestations and their utility in viral studies. Here, we created and compared hACE2 mouse models generated with different strategies. Our findings show that distinct β‐globin insertion within hACE2 cassette significantly influences its expression, with downstream placement enhancing transcription. Moreover, optimizing hACE2 codons (opt‐hACE2) improves translation efficiency in multiple tissues. Notably, opt‐hACE2 mice displayed more active immune responses and severe COVID‐19 phenotypes following SARS‐CoV‐2 challenge compared to other models. Our study demonstrates the dual regulatory role of β‐globin element in transgene transcription and suggests that opt‐hACE2 mice might serve as valuable tools for SARS‐CoV‐2 research.https://doi.org/10.1002/2211-5463.13934COVID‐19hACE2mouse modelβ‐globin |
| spellingShingle | Sun Jiaoyang Cheng Shaofei Hong Guangliang Quan Xiongzhi Lin Haofeng Mao Rui Johannes Grillari Shi Zheng‐Li Chen Jiekai Liu Meiqin Wu Haoyu Wu Guangming Enhancing human ACE2 expression in mouse models to improve COVID‐19 research FEBS Open Bio COVID‐19 hACE2 mouse model β‐globin |
| title | Enhancing human ACE2 expression in mouse models to improve COVID‐19 research |
| title_full | Enhancing human ACE2 expression in mouse models to improve COVID‐19 research |
| title_fullStr | Enhancing human ACE2 expression in mouse models to improve COVID‐19 research |
| title_full_unstemmed | Enhancing human ACE2 expression in mouse models to improve COVID‐19 research |
| title_short | Enhancing human ACE2 expression in mouse models to improve COVID‐19 research |
| title_sort | enhancing human ace2 expression in mouse models to improve covid 19 research |
| topic | COVID‐19 hACE2 mouse model β‐globin |
| url | https://doi.org/10.1002/2211-5463.13934 |
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