Document Type
Article
Publication Date
10-24-2024
Original Citation
Baker C,
Duso D,
Kothapalli N,
Hart T,
Casey S,
Cookenham T,
Kummer L,
Hvizdos J,
Lanzer K,
Vats P,
Shanbhag P,
Bell I,
Tighe M,
Travis K,
Szaba F,
Harder JM,
Bedard O,
Oberding N,
Ward J,
Adams M,
Lutz C,
Bradrick S,
Reiley W,
Rosenthal N.
Characterization of Collaborative Cross mouse founder strain CAST/EiJ as a novel model for lethal COVID-19. Sci Rep. 2024;14(1):25147.
Keywords
JGM, JMG, Animals, COVID-19, Disease Models, Animal, Mice, SARS-CoV-2, Lung, Collaborative Cross Mice, Viral Load, Female, Cytokines, Humans, Male
JAX Source
Sci Rep. 2024;14(1):25147.
ISSN
2045-2322
PMID
39448712
DOI
https://doi.org/10.1038/s41598-024-77087-1
Grant
Funding was provided by a grant to the Special Mouse Strain Resources at The Jackson Laboratory from the Na- tional Institutes of Health (NIH), Office of Research Infrastructure Programs (P40 OD011102) and by support from the F. M. Kirby Foundation and Anonymous Family Fund to the Trudeau Institute.
Abstract
Mutations in SARS-CoV-2 variants of concern (VOCs) have expanded the viral host range beyond primates, and a few other mammals, to mice, affording the opportunity to exploit genetically diverse mouse panels to model the broad spectrum of responses to infection in patient populations. Here we surveyed responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains. Infection of wild-derived CC founder strains produced a broad range of viral burden, disease susceptibility and survival, whereas most other strains were resistant to disease despite measurable lung viral titers. In particular, CAST/EiJ, a wild-derived strain, developed high lung viral burdens, more severe lung pathology than seen in other CC strains, and a dysregulated cytokine profile resulting in morbidity and mortality. These inbred mouse strains may serve as a valuable platform to evaluate therapeutic countermeasures against severe COVID-19 and other coronavirus pandemics in the future.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.