Groundbreaking Discovery

Introduction to CAST/EiJ Mouse Strain

In an exciting advance for infectious disease research, scientists at The Jackson Laboratory and the Trudeau Institute have announced the identification of the first mouse strain, known as CAST/EiJ, that is susceptible to severe COVID-19 without requiring any genetic modifications. This game-changing discovery was published in the journal Scientific Reports and is set to enhance the development of vaccines and therapeutics to combat future coronavirus variants and potentially mitigate pandemics.

Susceptibility and Response to SARS-CoV-2

What sets the CAST mouse apart from other strains is its extreme response to infection by SARS-CoV-2, encompassing the beta, omicron, and delta variants. While many common mouse strains showed either minimal symptoms or full recovery from the virus, the CAST mice exhibited alarming acute symptoms and acute illness, showcasing a lethal susceptibility to the virus.

Nadia Rosenthal, scientific director and professor at JAX, expressed the significance of this finding: "While most mouse strains display negligible reactions to SARS-CoV-2 variants, CAST mice respond lethally, offering an invaluable opportunity to understand the virus's impacts and to test innovative therapies."

Genetic Purity and Model Reliability

Originally captured from the island of Castania in 1971, CAST mice were bred at JAX to maintain a genetically pure lineage, ensuring a model closely representative of the mouse genome. This authenticity allows researchers a reliable platform to explore severe COVID-19 symptoms in a clean genetic background.

Lung Damage and Viral Load

One of the most concerning features of CAST mice is their ability to carry high viral loads within their lungs and the visible severe lung damage they suffer, mimicking the hyper-inflammatory responses observed in severely affected human patients. Unlike previous models, this strain avoids complications associated with brain infections, making it a superior model for studying the human immune response to COVID-19.

Promising Initial Trials

Excitingly, initial trials using antiviral treatments have generated promising results, improving survival rates among CAST mice. This brings hope that these mice could significantly contribute to developing effective therapies aimed at combating future coronavirus outbreaks. As new variants continue to emerge, the CAST mouse model positions researchers to respond quickly and effectively, potentially saving countless lives.

A Diverse Approach to Research

The study not only highlighted the uniqueness of CAST mice but also investigated a panel of eight genetically diverse mouse strains: A/J, B6J, CAST, 129S1, NSG, NZO, PWK, and WSB. Each strain harbors different genetic traits such as susceptibility to type 1 and type 2 diabetes, obesity, and leanness, which provided researchers with critical insights into the varied responses to viral infection.

Research leaders Rosenthal and Candice Baker, director of research projects at JAX, began with all eight strains and concluded that the CAST mouse's extraordinary susceptibility to SARS-CoV-2 was unmatched. They noted that while some strains recover from the virus, others experience lingering symptoms akin to those of long-COVID.

"We gained valuable insights into the acute symptoms of COVID-19 with CAST mice, and now our focus will pivot towards understanding the long-term effects," remarked Baker.

Future Research Plans

Future research plans for Rosenthal and Baker include investigating the long-term impacts of COVID-19 using the same panel of mouse strains, underscoring the need for comprehensive studies in this evolving field.

Breaking Down Barriers in COVID-19 Research

When the pandemic first surfaced, traditional mouse models were inadequate for studying SARS-CoV-2 due to the absence of necessary receptors for viral binding. In 2023, Rosenthal and her team sought to address this problem through engineered mice that featured human receptors; however, the severity of infections in these models did not accurately reflect the variety of human responses to the virus.

By blending genetically engineered mice with diverse strains, Rosenthal’s team succeeded in mimicking a range of human-like responses. Unlike these earlier models, CAST mice do not require artificial receptor modifications, which fosters a more authentic scenario for studying severe COVID-19.

Implications for Future Research

"CAST mice are positioned to significantly advance COVID-19 research and prepare us for future challenges," Rosenthal emphasized. "The research also stresses the imperative of genetic diversity in scientific study, opening new doors in our fight against infectious diseases."

With the potential to transform our understanding of COVID-19 and other future viruses, the CAST mouse strain may become an essential tool in safeguarding global health.