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Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression.

ABSTRACT: How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified in various settings. Herein we use RNA-Seq data and bioinformatics approaches to analyze the transcriptional responses in SARS-CoV-2 infected lungs, comparing 4 human studies with the widely used K18-hACE2 mouse model, a model where hACE2 is expressed from the mouse ACE2 promoter, and a model that uses a mouse adapted virus and wild-type mice. Overlap of single copy orthologue differentially expressed genes (scoDEGs) between human and mouse studies was generally poor (≈15-35%). Rather than being associated with batch, sample treatment, viral load, lung damage or mouse model, the poor overlaps were primarily due to scoDEG expression differences between species. Importantly, analyses of immune signatures and inflammatory pathways illustrated highly significant concordances between species. As immunity and immunopathology are the focus of most studies, these mouse models can thus be viewed as representative and relevant models of COVID-19.

SUBMITTER: Bishop CR

PROVIDER: S-EPMC9536645 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression.

Bishop Cameron R CR Dumenil Troy T Rawle Daniel J DJ Le Thuy T TT Yan Kexin K Tang Bing B Hartel Gunter G Suhrbier Andreas A

PLoS pathogens 20220926 9

How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified in various settings. Herein we use RNA-Seq data and bioinformatics approaches to analyze the transcriptional responses in SARS-CoV-2 infected lungs, comparing 4 human studies with the widely used K18-hACE2 mouse model, a model where hACE2 is expressed from the mouse ACE2 promoter, and a model that uses a mouse adapted virus and wild-type mice. Overlap ...[more]

PMID: 36155667

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Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression.

Publications

Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression.

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