The Jackson Laboratory Knockout Mouse Production and Phenotyping Project (JAX KOMP2)

NIH Pandemic-Era Grants

Pandemic Era Grants

2020

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Principal Investigator: ROBERT E BRAUN
Organization: JACKSON LABORATORY
Fiscal Year: 2020
Award: $925,466
Funding agency: NIH Office of the Director

PROJECT SUMMARY
In response to “NOT-RM-20-015”, we propose an urgent competitive revision to The Jackson Laboratory
Knockout Mouse Phenotyping Project (KOMP2) to develop the next generation of precision mouse models for
mechanistic discovery of SARS-CoV2 infection and therapeutic discovery of COVID-19 disease treatments.
The worldwide response to the COVID-19 pandemic has triggered a surge in demand for animal models to
understand the underlying biology and pathology of SARS-CoV-2 infection and for the preclinical development
of novel therapeutic strategies. Several mouse models have recently been reported that respond with varying
degrees to SARS-CoV-2 infection. However, given the diversity of patient outcomes, any one mouse model on
a standard inbred genetic background does not reflect the impact of host genetic context on SARS-CoV-2
infection and response to treatment. We therefore propose to create a second-generation mouse model
platform incorporating diverse genetic backgrounds, to characterize the variation in SARS-CoV-2 infection
dynamics and the development of clinically-relevant disease. The proposed project will rapidly provide the
research community with an urgently needed resource for linking the variability in COVID-19 disease outcome
with underlying host genetic features, and for developing precision therapies tailored to treat the individual
patient. Our Specific Aims are: 1) To create a panel of genetically diverse transgenic models for SARS-CoV-2
infection; 2) To characterize infectivity, phenotypic response, disease outcome, and transcriptome
heterogeneity of these models; and 3) To distribute these models and our outcome data to the scientific
community.

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