Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression [article]

Cameron R Bishop, Troy Dumenil, Daniel J Rawle, Thuy Le, Kexin Yan, Bing Tang, Gunter Hartel, Andreas Suhrbier
2022 bioRxiv   pre-print
BACKGROUND: How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified in various settings. The K18-hACE2 mouse model has been widely used for evaluation of new interventions for COVID-19. METHOD. Herein we use RNA-Seq data and bioinformatics approaches to compare the transcriptional responses in the SARS-CoV-2 infected lungs of K18-hACE2 mice with those seen in humans. RESULTS: Overlap in differentially
more » ... ssed genes was generally poor (≈20-30%), even when multiple studies were combined. The overlap was not substantially improved when a second mouse model was examined wherein hACE was expressed from the mouse ACE2 promoter. In contrast, analyses of immune signatures and inflammatory pathways illustrated highly significant concordances between the species. CONCLUSION: As immunity and immunopathology are the focus of most studies, these hACE2 transgenic mouse models can thus be viewed as representative and relevant models of COVID-19.
doi:10.1101/2022.02.24.481866 fatcat:q3cjp5q5q5gwdjdepooehzz2uq