Commentary - (2021) Volume 0, Issue 0
The continuing COVID-19 pandemic, caused by SARS-CoV-2, has spurred heightened urgency for new therapeutics. In turn this has underscored the need for better animal models to use for both research and development. A recent commentary in Biochemical Pharmacology by Jarnagin et al. has proposed a three gene humanized mouse model to serve this need.
Covid-19 • Sars-Cov-2 • Biochemical
SARS-CoV-2 causes a mild infection in most patients. However, in those patients with underlying medical conditions the disease can be devastating leading to hospitalization and in some cases, death [1,2]. Various animal species have been investigated as models for infection and disease, but none fully recapitulate the range of symptoms and disease seen in man [3]. The mouse is by far, the most popular animal model for research in immunology, small molecule and antibody-based drugs as well as vaccine development [4,5]. Unfortunately, the human receptor for SARS-CoV-2, ACE2 is not equivalent to mouse ACE2. This led Jernigan et al., [6] to propose the development of a new mouse model that would be an improvement over what is currently available.
The new mouse model outlines the construction of two different strains of mice containing human ACE2 and TMPRSS2 (the protease that is involved in viral entry) or ACE2, TMPRSS2, and FCGRT (the receptor that binds antibodies and controls antibody half-life in circulation) on two mouse genetic backgrounds (C57Bl/6J; Th1-biased immune response and BALB/c; Th2-biased immune response). These genetic constructs interrupt the equivalent mouse genes so that only the human gene is expressed under the control of the relevant mouse promoters. This ensures that only the human gene is expressed (an improvement over current mouse models) and that it is expressed in tissues in the proper manner. The two different mouse genetic backgrounds will allow investigators to model a wide spectrum of diseases ranging from mild to severe COVID-19. The FCGRT humanized mice will allow researchers to develop and test antibody-based therapies, as antibodies as a therapeutic class have many unique advantages.
As SARS-CoV-2 is mutating rapidly and causing additional waves of the pandemic, and the world is facing a massive public health burden posed by a constellation of “long” COVID syndromes, there is an urgent need to improve on currently available mouse models to study SARS-CoV-2 infections and develop new therapeutics. The authors have outlined how such improvements might be done. As of this writing, the construction of such mice is well advanced towards its goal.
Citation: Webb DR Jarnagin K, Shresta S. A New Mouse Model for COVID-19 Research and Development. Med Rep Case Stud, 2021,06(S2):001.
Received: 11-May-2021 Published: 01-Jun-2021
Copyright: © 2021 Webb DR, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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