# MMRRC COVID-19 variant testing in humanized mouse models

> **NIH NIH U42** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $498,821

## Abstract

ABSTRACT & SCOPE OF WORK
The Mutant Mouse Resource and Research Center at the University of California, Davis (MMRRC-UC Davis)
is pleased to submit this administrative supplement for up to 1 year of support in response to ORIP’s
participation in PA-20-272, “Administrative Supplements to Existing NIH Grants and Cooperative Agreements”
specifically related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19).
This application addresses a number of the stated objectives of the call to support COVID-19 related research,
including to develop and characterize animal models for post-acute sequelae of COVID-19 (PASC) and to
study the susceptibility of existing COVID-19 animal models to emerging viral genomic variants. Specifically,
this application will generate polygenic humanized mouse models for virus challenge, validation, and post-
acute sequellae of COVID-19 (PASC) in both young and aging mice using well-established testing and
screening platforms in an ABSL3 environment. This project will build upon our successful efforts to generate
monogenic humanized knockin/murine knockout mouse lines for several genes (ACE2, TMPRSS2, and
FURIN) involved in SARS-CoV-2 binding, entry, and activation. With this prior experience in hand, we now
propose to determine infectivity and transmission in new polygenic humanized mice to assess the extent to
which they can be used as suitable models of PASC in humans. Specifically in this project we will 1) use in
vitro fertilization (IVF) expansion and intercrossing of our extant monogenic models to rapidly generate
polygenic humanized mouse models of hACE2/hTMPRSS2 and hACE2/hTMPRSS2/hFURIN, 2) validate the
pathophysiological effects and assess PASC after challenge with currently dominant circulating (B.1.1.7; strain:
USA/CA_CDC_5574/2020) in young and aging male and female cohorts of polygenic humanized mice under
ABSL3 conditions, and 3) establish breeding colonies and cryopreserved germplasm of humanized mouse
models for archiving and distribution to the biomedical research community. Validation studies will involve
systematic characterization of viral load and clearance, body weight kinetics, and lung inflammation after
SARS-CoV-2 challenge of male and female cohorts of mice; positive results will be communicated to the
ACTIV-Preclinical Working Group and others at NIH. In addition, observational and pathological screening of
surviving aging mice will be conducted to screen for evidence of PASC; promising findings will be
communicated with members of the PASC Initiative and Investigator Consortium (OTA-21-015A and B) and
other NIH staff to ensure rapid translation of findings for human studies and functional studies in animal
models. Further, we will ensure that our mouse models and testing platform will be made readily available for
use by other researchers to swiftly assess the in vivo consequences of not only newly appearing SARS-CoV-2
variants that escape current therapeutic and vacc...

## Key facts

- **NIH application ID:** 10412858
- **Project number:** 3U42OD012210-22S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** KC KENT LLOYD
- **Activity code:** U42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $498,821
- **Award type:** 3
- **Project period:** 2021-07-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412858

## Citation

> US National Institutes of Health, RePORTER application 10412858, MMRRC COVID-19 variant testing in humanized mouse models (3U42OD012210-22S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10412858. Licensed CC0.

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