COVID-19 - Coronavirus disease 2019

Development of mouse models of COVID-19 – HuMoCID

Submission summary

Research on COVID-19 is currently hampered by the delayed availability and lack of diversity of small rodent models of SARS-CoV-2 infection. Wildtype mice are poorly susceptible to this virus due to the sequence divergence between the mouse and the human in the ACE2 gene which acts as the virus receptor.
Here, we propose to develop two types of mouse models expressing the human ACE2 (hACE2) gene. First, we will transduce cells of the respiratory tract of mice using a defective adenovirus containing the hACE2 gene. This strategy, which has been used successfully with MERS-CoV, will yield susceptible mice in less than two months and could be used to assess quickly vaccine candidates. Second, we will produce novel transgenic strains expressing the hACE2 gene either in the respiratory tract or ubiquitously. This will yield mouse strains that are constitutively susceptible and that are easily expandable and distributable to the scientific community.
Furthermore, to refine these models and to investigate how host genes can modify the severity of the illness caused by SARS-CoV-2 infection, we will combine these models with the genetic diversity of a state-of-the-art genetic resource, the Collaborative Cross. This strategy will expand the range of mouse models to better reproduce the clinical diversity of COVID-19 observed in humans.

Project coordinator

Monsieur Xavier MONTAGUTELLI (Laboratoire Génétique de la Souris)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Génomique Evolutive des Vrus à ARN, Institut Pasteur
Unité de Neuropathologie Expérimentale, Institut Pasteur
Centre d'Ingénerie Génétique Murine, Institut Pasteur
Unité de Virologie Moléculaire et Vaccinologie, Institut Pasteur
Laboratoire Génétique de la Souris

Help of the ANR 147,528 euros
Beginning and duration of the scientific project: March 2020 - 18 Months

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