Animal models for SARS-Cov2/Covid19 research-A commentary

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Current animal models for SARS-CoV-2 infection inadequately replicate human COVID-19 clinical features, often resulting in milder disease.
• Existing transgenic models with random gene integration exhibit unnatural expression and rapid lethality, limiting their research utility.

Purpose of the Study:

• To propose improved precision humanized mouse models for SARS-CoV-2 research.
• To enhance understanding of COVID-19 pathogenesis, immunity, and therapeutic efficacy.

Main Methods:

• Suggesting precision knock-in of human mini genes (ACE2, TMPRSS2, FcγRT) at mouse initiation codons with homologous gene knockout.
• Proposing the creation of single, double, and triple humanized gene combinations.
• Developing these models on C57BL/6J (Th1) and BALB/c (Th2) backgrounds to mimic human immune responses and pathology.

Main Results:

• Precision humanized mouse models are expected to provide superior platforms compared to current transgenic models.
• These models will allow detailed investigation of receptor and coreceptor roles in infection and therapeutic response.
• The models will facilitate the study of diverse human COVID-19 pathologies, including lung issues and long-term effects.

Conclusions:

• Precision humanized mouse models represent a significant advancement for COVID-19 research.
• These models will serve as state-of-the-art tools for investigating pathogenesis, immunity, and developing vaccines and drugs.
• Thorough characterization of these models at multiple levels is essential for maximizing their research potential.