Generating Novel Humanized Mouse Models for in vivo COVID19 Mechanism Studies and Therapeutics Tests

NIH Pandemic-Era Grants

Pandemic Era Grants

2020

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Principal Investigator: Jamie M Verheyden
Organization: UNIVERSITY OF CALIFORNIA, SAN DIEGO
Fiscal Year: 2020
Award: $434,000
Funding agency: National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY
 The COVID19 pandemic has spread across the globe with unprecedented speed and
devastation. With infected individuals rising past 1.4 million in the US, there is a dizzying
amount of information causing confusion around which tissues SARS-CoV-2 infects and how it
triggers catastrophic immune response and tissue destruction. Furthermore, with the rapidly
increasing number of candidate therapies, there is an urgent need for animal models that
faithfully recapitulate the human disease and is scalable to provide power for preclinical testing.
 We will use our extensive expertise in mouse genetics to generate two novel mouse models
that express human viral receptor ACE2 (hACE2) in either selected cell types/tissues of interest
or in the endogenous pattern of ACE2 expression in mice. Expression of the hACE2 gene will
allow efficient SARS-CoV-2 infection. We will use infected humanized mice to dissect the
progression of COVID19 from initial infection of host cells, to antiviral and pro-inflammatory
responses, to development of acute respiratory distress syndrome, using single cell approaches
such as single cell RNAseq. In parallel, we will also use infected humanized mice to test the
effectiveness of candidate FDA approved drugs for their effectiveness in halting COVID19. We
expect that these humanized mouse models will be valuable platforms for a large number of
COVID research directions listed as Areas of High Priority in PAR-20-177.

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