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Related Experiment Video

Updated: Dec 3, 2025

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Genetically modified mouse models to help fight COVID-19.

Channabasavaiah B Gurumurthy1,2, Rolen M Quadros3, Guy P Richardson4

  • 1Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA. cgurumurthy@unmc.edu.

Nature Protocols
|October 27, 2020
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Summary

Developing genetically engineered mouse models is crucial for understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and creating COVID-19 treatments. These models overcome wild-type mouse resistance to the virus.

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Area of Science:

  • * Virology and Immunology
  • * Genetics and Genomics
  • * Preclinical Disease Modeling

Background:

  • * Understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mechanisms is critical for developing effective therapies and vaccines for coronavirus disease 2019 (COVID-19).
  • * A significant hurdle in COVID-19 research is the lack of appropriate preclinical animal models, as wild-type mice are naturally resistant to SARS-CoV-2 infection.
  • * Mice are extensively used in biomedical research, and genetic modification tools are readily available for them.

Purpose of the Study:

  • * To address the need for suitable animal models in COVID-19 research.
  • * To propose the development of genetically engineered mouse models (GEMMs) that express human ACE2, enabling SARS-CoV-2 infection.
  • * To outline versatile GEMM designs for advancing SARS-CoV-2 research and therapeutic development.

Main Methods:

  • * Leveraging existing genetic tools for mouse modification.
  • * Designing models to express human angiotensin-converting enzyme 2 (ACE2) to facilitate viral entry.
  • * Proposing three broad categories and over two dozen specific designs for GEMMs.

Main Results:

  • * Genetically engineered mice expressing human ACE2 are susceptible to SARS-CoV-2 infection.
  • * The proposed models provide a platform for studying viral pathogenesis and testing interventions.
  • * A diverse range of GEMM designs can be created to model various aspects of COVID-19.

Conclusions:

  • * Genetically engineered mouse models are essential for overcoming the limitations of wild-type mice in SARS-CoV-2 research.
  • * These models will accelerate the understanding of COVID-19 molecular mechanisms, drug repurposing, and vaccine development.
  • * The proposed GEMMs offer a valuable resource for the global research community in the fight against COVID-19.