Lead Investigator: Andreas Suhrbier, QIMR Berghofer Medical Research institute
Title of Proposal Research: The K18 mouse model recapitulates the transcriptomic response to acute COVID-19 Acute Respiratory Distress syndrome (ARDS) in humans
Vivli Data Request: 6734
Funding Source: A.S. holds an Investigator grant from the National Health and Medical Research Council (NHMRC) of Australia (APP1173880)
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Mice are not naturally susceptible to infection with SARS-Cov2, the infectious agent that causes COVID-19. This is due to a structural difference in a key protein, angiotensin-converting enzyme 2 (ACE-2), which is required for cellular-entry during infection with SARS-Cov2. Since mouse models are an important resource for studying the pathophysiology of COVID-19, several genetically modified mouse models have been developed to express the human orthologue of ACE-2 (hACE-2). The K18 mouse strain is genetically modified to express hACE-2 via a cytokeratin-18 (K18) gene promoter. A recent study using the K18 mouse model reported that SARS-Cov2 infected the lungs and caused an inflammatory response similar to that observed in humans. In the current study we infected K18 mice with SARS-Cov2 to investigate the transcriptional response during the acute phase of infection, and to compare these results with the transcriptional response in humans. The results of this study will serve as an evaluation of the K18 mouse model in terms of its ability to recapitulate acute COVID-19 infection in humans.
Statistical Analysis Plan:
RNA-Seq data will be analyzed using a bioinformatics pipeline to produce a list of differentially expressed genes. Expression data will then be subjected to a Gene Set Enrichment Analysis (GSEA) and pathway analysis.
Requested Studies:
COVID-19: Pulmonary Vascular Endothelialitis, Thrombosis and Angiogenesis
Sponsor: Hannover Medical School
Public Disclosures:
Bishop CR, Dumenil T, Rawle DJ, Le TT, Yan K, et al. Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression. (2022). PLOS Pathogens 18(9): e1010867. Doi: 10.1371/journal.ppat.1010867