Enhancing human <scp>ACE2</scp> expression in mouse models to improve <scp>COVID</scp> ‐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 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.
Authors
- Xiongzhi Quan
- Johannes Grillari (ORCID: https://orcid.org/0000-0001-5474-6332)
- Chen Jiekai
- Haoyu Wu (ORCID: https://orcid.org/0000-0002-8995-3486)
- Rui Mao (ORCID: https://orcid.org/0000-0002-2374-5406)
- Sun Jiaoyang
- Lin Haofeng
- Wu Guangming
- Hong Guangliang
- Zheng‐Li Shi (ORCID: https://orcid.org/0000-0001-8089-163X)
- Liu Meiqin
- Cheng Shaofei
Institutions
- Institute of Molecular Biotechnology (AT)
- Chinese Academy of Sciences (CN)
- Guangzhou Institutes of Biomedicine and Health (CN)
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA (AT)
- First Affiliated Hospital of Guangzhou Medical University (CN)
- Wuhan Institute of Virology (CN)
- Austrian Cluster for Tissue Regeneration (AT)
- University of Chinese Academy of Sciences (CN)
- Ludwig Boltzmann Institute for Digital Health and Prevention (AT)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- FEBS Open Bio
- Published
- 2024-12-29
- DOI
- https://doi.org/10.1002/2211-5463.13934
- Citations
- 1
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.39
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Austrian Science Fund
- Herzfelder'sche Familienstiftung
- OeAD-GmbH
- Medizinischen Hochschule Hannover
- Guangdong Provincial Pearl River Talents Program
- National Key Research and Development Program of China
- Science and Technology Planning Project of Guangdong Province
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences