In recent years, it has become evident that young individuals generally face a reduced risk of severe illness or fatality when infected with COVID-19 in comparison to older age groups. While the underlying factors behind this observation remain uncertain, researchers have made a groundbreaking achievement by successfully replicating this phenomenon in mice for the first time.
Creating First-Ever Mouse Model
Scientists have employed genetic modifications to introduce a human-like variant of COVID-19 to mice, enabling them to manifest symptoms closely resembling those observed in young human patients.
Interesting Engineering reported that this represents a significant departure from prior mouse models that succumbed to the infection.
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A field mouse is pictured in Saint-Philbert-sur-Risle on August 1, 2023.
The research led by Jef Boeke, who is the Sol and Judith Bergstein Director at NYU Langone Health's Institute for Systems Genetics, emphasized the significance of this breakthrough.
He pointed out that the survival of the genetically altered mice represents a major step in creating an animal model that faithfully mirrors the way COVID-19 manifests in most human cases.
That includes how it activates immune system cells and leads to comparable symptoms. The achievement addresses a critical gap in the quest for new antiviral medications targeting this virus. Researchers achieved this by creating laboratory mice with human genetic material linked to Angiotensin-Converting Enzyme 2 (ACE2).
ACE2 is a protein present in various human cell types, playing a vital role in the Renin-Angiotensin System (RAS), which regulates essential functions like blood pressure, fluid balance, and electrolyte levels.
Development, Progression of COVID-19
Of particular significance, ACE2 has gained substantial attention in the context of the COVID-19 pandemic. That is because it serves as the primary entry point for the SARS-CoV-2 virus, which is responsible for causing COVID-19, into human cells.
The virus' spike protein binds to ACE2 receptors on the host cell's surface, enabling the virus' entry and subsequent infection. The interaction between the virus and ACE2 holds significant implications for the development and progression of COVID-19.
It is a fundamental factor in how the virus impacts crucial human cells, leading to the manifestation of symptoms and complications associated with the disease.
In recent years, the extensive research into ACE2 and its connection to SARS-CoV-2 has been pivotal in unraveling the mechanisms behind the virus' transmission and has played a crucial role in the advancement of therapies and vaccines for COVID-19.
Boeke and his team look forward to exploring the potential of crossbreeding these humanized ACE2 mice with a wide array of existing mouse strains, which will facilitate the study of varied responses to the virus, particularly in individuals with health conditions like diabetes or obesity, as well as in the context of aging.
To address the complexities of human genetics, Boeke's lab originally devised the "genome writing" technique using yeast, a single-celled fungus with attributes similar to human cells, yet simpler and more conducive to research.
This novel approach allowed the research team to successfully engineer live mice with cellular properties closely resembling the ACE gene activity levels found in humans.
The research findings, which mark a significant advancement in the understanding of COVID-19, have been comprehensively documented in the journal Nature.
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