# A novel model to study COVID-19 and Hypertension > **NIH NIH R21** · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · 2021 · $231,750 ## 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:** 10287008 - **Project number:** 1R21AI164449-01 - **Recipient organization:** UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS - **Principal Investigator:** BINA JOE - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $231,750 - **Award type:** 1 - **Project period:** 2021-06-14 → 2023-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10287008 ## Citation > US National Institutes of Health, RePORTER application 10287008, A novel model to study COVID-19 and Hypertension (1R21AI164449-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10287008. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*