Generation of a humanized mAce2 and a conditional hACE2 mouse models permissive to SARS-COV-2 infection

I. Wen Song, Megan Washington, Carolina Leynes, Jason Hsu, Kempaiah Rayavara, Yangjin Bae, Nele Haelterman, Yuqing Chen, Ming Ming Jiang, Aleksandra Drelich, Vivian Tat, Denise G. Lanza, Isabel Lorenzo, Jason D. Heaney, Chien Te Kent Tseng, Brendan Lee, Ronit Marom

Research output: Contribution to journalArticlepeer-review

Abstract

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains a public health concern and a subject of active research effort. Development of pre-clinical animal models is critical to study viral-host interaction, tissue tropism, disease mechanisms, therapeutic approaches, and long-term sequelae of infection. Here, we report two mouse models for studying SARS-CoV-2: A knock-in mAce2F83Y,H353K mouse that expresses a mouse-human hybrid form of the angiotensin-converting enzyme 2 (ACE2) receptor under the endogenous mouse Ace2 promoter, and a Rosa26 conditional knock-in mouse carrying the human ACE2 allele (Rosa26hACE2). Although the mAce2F83Y,H353K mice were susceptible to intranasal inoculation with SARS-CoV-2, they did not show gross phenotypic abnormalities. Next, we generated a Rosa26hACE2;CMV-Cre mouse line that ubiquitously expresses the human ACE2 receptor. By day 3 post infection with SARS-CoV-2, Rosa26hACE2;CMV-Cre mice showed significant weight loss, a variable degree of alveolar wall thickening and reduced survival rates. Viral load measurements confirmed inoculation in lung and brain tissues of infected Rosa26hACE2;CMV-Cre mice. The phenotypic spectrum displayed by our different mouse models translates to the broad range of clinical symptoms seen in the human patients and can serve as a resource for the community to model and explore both treatment strategies and long-term consequences of SARS-CoV-2 infection.

Original languageEnglish (US)
JournalMammalian Genome
DOIs
StateAccepted/In press - 2024
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

Fingerprint

Dive into the research topics of 'Generation of a humanized mAce2 and a conditional hACE2 mouse models permissive to SARS-COV-2 infection'. Together they form a unique fingerprint.

Cite this