Researchers at The Jackson Laboratory and Trudeau Institute have made a groundbreaking discovery by identifying the first mouse strain that is susceptible to severe COVID-19 without the need for genetic modification. This significant development, published in Scientific Reports, represents a crucial advancement in infectious disease research and provides a vital tool for the development of vaccines and therapeutics for future coronavirus variants and potential pandemics.
The CAST/EiJ mouse, part of a research panel consisting of eight genetically diverse mouse strains, has shown a severe response to SARS-CoV-2 infection, including beta, omicron, and delta variants. While other mouse strains either recovered from the infection or displayed mild symptoms, the CAST mice exhibited acute illness, showcasing their unique susceptibility to the virus.
Nadia Rosenthal, scientific director and professor at JAX, and one of the senior authors of the study, emphasized the significance of the CAST mice in understanding the lethal response to SARS-CoV-2 variants. These mice provide a valuable resource for studying the virus’s impact and testing new therapies.
Originating from the island of Castania and brought to JAX in 1971, CAST mice have been carefully bred to maintain a genetically pure line, making them an ideal model for investigating severe COVID-19 symptoms on a clean genetic background. These mice not only carry high viral loads in their lungs but also exhibit severe lung damage, resembling the hyperinflammatory response seen in severe COVID-19 cases in humans.
Preliminary trials using antiviral treatments have shown promising results in boosting survival rates in CAST mice, offering hope for the development of therapies for future coronavirus outbreaks. As new variants continue to emerge, the CAST mouse model stands poised to accelerate research efforts and provide insights that could potentially save lives.
The study also explored eight genetically diverse mouse strains, each with unique traits such as susceptibility to diabetes, obesity, and leanness. The diverse genetic backgrounds allowed researchers to uncover differences in virus susceptibility, with the CAST mouse emerging as highly susceptible to SARS-CoV-2 infection.
Moving forward, Rosenthal and Candice Baker, director of research projects at JAX, plan to investigate the long-term effects of COVID-19 using the panel of eight mouse strains. This research will provide valuable insights into both acute and lingering symptoms of the disease.
The development of the CAST mouse model overcomes the early challenges faced in COVID-19 research, where traditional mouse models were unsuitable for studying the virus. By leveraging the genetic diversity of mouse strains, researchers have created a more natural and clinically relevant model for studying severe COVID-19.
In conclusion, the identification of the CAST mouse as the first mouse strain susceptible to severe COVID-19 without genetic modification represents a significant milestone in infectious disease research. This model offers a valuable tool for studying the virus’s impact, testing new therapies, and preparing for future challenges posed by emerging coronavirus variants. The work reinforces the critical role of genetic diversity in scientific research and underscores the potential of mouse models in advancing our understanding of infectious diseases.
