A recent study led by researchers at The Jackson Laboratory and Trudeau Institute has identified the first mouse strain that is naturally susceptible to severe COVID-19 without the need for genetic modification. This groundbreaking discovery, published in Scientific Reports, provides important insights into vaccine and therapeutic developments against current and future coronavirus variants.

The Unique CAST Mouse Strain

The study focused on a panel of eight genetically diverse mouse strains, including A/J, B6J, CAST, 129S1, NSG, NZO, PWK, and WSB. Among these, only the CAST/EiJ mouse exhibited a severe response to SARS-CoV-2, encompassing the beta, omicron, and delta variants. The diverse traits represented by these strains include susceptibility to type 1 and type 2 diabetes, obesity, and leanness.

While most of the other strains either recovered or exhibited milder symptoms, the CAST mice demonstrated acute illness symptoms, including:

  • High viral loads in the lungs: indicating significant replication of the virus.
  • Severe lung damage: Marked by hyperinflammatory responses akin to those observed in human patients.
  • Non-recoverability: Most CAST mice did not recover from severe symptoms.

Advancements in COVID-19 Research

According to Nadia Rosenthal, scientific director and professor at JAX, CAST mice represent an invaluable resource for studying COVID-19 due to their lethal response to infection. “Although most mice strains show negligible symptoms from SARS-CoV-2 variants, CAST mice provide a much closer parallel to the human immune response, particularly in severe cases,” she noted.

Initial Findings and Future Directions

Initial antiviral treatment trials on CAST mice have shown promising results, increasing their survival rates. This enhances their potential role in developing therapies aimed at future coronavirus outbreaks. The study also emphasizes the need for continued examination of long-term effects of COVID-19 infection. Rosenthal and co-author Candice Baker plan to pursue further investigations into these impacts using the same panel of mouse strains.

Challenges Overcome in COVID-19 Research

At the onset of the pandemic, traditional mouse models were inadequate for SARS-CoV-2 research due to the absence of necessary receptors. Prior attempts in 2023 to address this limitation involved genetically engineered mice with human-like receptors, which, unfortunately, resulted in overly acute infections not reflective of human variability. The identification of the CAST mouse offers a more representative model devoid of artificial modifications.

“CAST mice stand poised to transform COVID-19 research and prepare us for future challenges,” said Rosenthal, emphasizing the essential role of genetic diversity in scientific exploration.

Diversity in Mouse Models

The study revealed vital genetic diversity across the mouse strains, significantly aiding the understanding of varying COVID-19 susceptibilities. The following table summarizes the eight mouse strains and their observed responses to SARS-CoV-2:

Mouse Strain Response to SARS-CoV-2
A/J Mild symptoms, full recovery
B6J Mild symptoms, full recovery
CAST/EiJ Severe illness, high mortality
129S1 Moderate recovery
NSG Mild symptoms, full recovery
NZO Mild symptoms, full recovery
PWK Mild symptoms, full recovery
WSB Mild symptoms, full recovery

Future Perspectives

This discovery of the CAST mouse strain offers researchers an unprecedented opportunity to better understand COVID-19 mechanisms and develop therapeutics aimed at improving patient outcomes. Lifespan.io underscores the necessity of utilizing genetic diversity to enhance biomedical research and combat current and future pandemics.

Conclusion

In summary, the identification of the CAST mouse strain as susceptible to severe COVID-19 marks a significant milestone in infectious disease research. The study not only highlights its potential for future vaccine and therapy development but also underscores the importance of genetic diversity within scientific research. Continued collaboration and research are essential for addressing the complexities of COVID-19 and preparing for emergent viral challenges.

References

Candice N. Baker et al, Characterization of Collaborative Cross mouse founder strain CAST/EiJ as a novel model for lethal COVID-19, Scientific Reports (2024).

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