# A novel model to study COVID-19 and Hypertension

> **NIH NIH R21** · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · 2022 · $193,125

## Abstract

7. Project Summary/Abstract
Animal models fare indispensable for understanding the pathology of COVID-19 as well as for developing
vaccines. They are also important to discern the etiology of COVID-19 in specific groups at risk, such as
individuals with pre-existing hypertension. While there are hamsters, ferrets, cats, nonhuman primates and K18-
hACE2 transgenic mice as possible models for studying COVID-19, none serves the purpose of studying the
relationship between hypertension and susceptibility to COVID-19 because (1) wild-type research models do not
get infected with the human SARS-CoV-2 and/or (2) they are not genetically prone to hypertension. To fill this
unmet need, we propose to develop in vivo experimental platform for studying COVID-19 in the setting of
hypertension. In preliminary data, we present evidence for the development of a novel knock-in rat model of the
hypertensive Dahl Salt-sensitive (S) rat edited using the CRISPR/Cas9 technology to express the human ACE2
gene (hACE2), which is the receptor for SARS-CoV-2. The gene hACE2 is inserted to replace the rat Ace2 locus.
The required rat Ace2 knockout as the control strain (rAce2-KO) has also been generated. By comparing these
2 strains, in Aim 1 we will examine the suitability of this rat model for studying COVID-19. Further, based on our
recent published work using germ-free rats indicating that introduction of microbiota to germ-free rats
upregulated colonic Ace2 expression and blood pressure combined with the existing knowledge of a strong
relationship between salt-sensitive hypertension and the gut microbiota; in Aim 2, we will test the hypothesis that
the loss of normal symbiosis between the host and gut microbiota during a hypertensive state is responsible for
the lower ACE2 expression in multiple organs.

## Key facts

- **NIH application ID:** 10428648
- **Project number:** 5R21AI164449-02
- **Recipient organization:** UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
- **Principal Investigator:** BINA JOE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $193,125
- **Award type:** 5
- **Project period:** 2021-06-14 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428648

## Citation

> US National Institutes of Health, RePORTER application 10428648, A novel model to study COVID-19 and Hypertension (5R21AI164449-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10428648. Licensed CC0.

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