COVID-19 Resource List for Researchers – ACE2 Animal Models and More

The pneumonia-like COVID-19 caused by the novel coronavirus (SARS-CoV-2) remains a huge medical challenge worldwide. To provide a wholistic guide for developing clinical treatments, vaccines, and antiviral drugs, it is of great significance to study the interaction mechanisms between severe acute respiratory syndrome (SARS) coronaviruses and host molecules, while also exploring the pathogenic process of coronaviruses. Accurate animal models are necessary for verifying the pathogenesis and immune mechanisms of the illness to accelerate research across vaccine development, new drug development, gene therapy, and more. 

Since the early stages of the pandemic, Cyagen has been creating Technical Bulletins that cover several developments in SARS-CoV-2 and COVID-19 research. Our Technical Bulletins are based on numerous publications and cover a multitude of topics, including: promising animal models used for SARS-CoV research, evidence regarding the cross-species transmission pathway, and the predominantly-targeted ACE2 host receptor that is involved in onset of viral infection by SARS-CoV-2 and the development of COVID-19.

Mouse Models for SARS - Construction Strategies and Applications

In studying human-infecting coronavirus diseases, the advantages of the mouse model compared to other in vivo models are readily apparent - lower cost, easy breeding, faster reproduction, and more litters. More importantly, the genetic background of inbred mice is consistent, permitting their genes to be edited to reliably construct the required models. Such custom models are used to study the role of specific host genes in pathogenic processes, as well as in understanding host immunity response and mechanisms of protection initiated by viral challenge. 

Species differences between mouse and human genomes influence viral pathology, resulting in some human-infecting viruses being unable to directly infect mice, or that mice exhibit no obvious symptoms even after in vivo virus replication. The mechanism of viral infection requires binding to specific host cell surface receptors, which influences the associated innate immune response of the host. In the case of SARS-CoV-2, the virus’ receptor binding motif (RBM) binds to human ACE2 receptors, but not endogenous mouse ACE2. Given that the genetic background of inbred mice is consistent, editing the mouse genes can overcome the shortcomings of wild-type mice to a certain extent. One noteworthy example is the development of humanized mouse models, which integrate human genes that are relevant to the pathology of interest. Such genetic engineering approaches help to elucidate the role of the host’s specific genes in viral pathogenesis, providing a mechanism for research across a range of applications - from investigating preliminary genetic targets, through evaluating the safety and efficacy of vaccines and drugs.

Advances in mouse models used to study the SARS-CoV-2 and COVID-19

Comparisons of both nucleic and amino acid sequences have confirmed a high similarity between SARS-CoV-2 and SARS-CoV - approximately 80% and 76%, respectively. Additionally, SARS-CoV-2 initiates infection through interactions with the human ACE2 receptor on the cell surface, causing clinical manifestations similar to SARS-CoV infection. Therefore, strategies and methods for constructing mouse models for SARS-CoV infection are also suitable for establishing SARS-CoV-2 infection mouse models. Scientists studying the novel coronavirus (SARS-CoV-2) and the resulting infection, known as COVID-19, have used the following mouse models with promising results:

1. Transgenic hACE2 Mouse Model
2. Targeted Insertion of hACE2-tdTomato Mouse Model
3. Model Developed with Adenovirus Vector – Ad5-hACE2 Mice

Visit the complete version to learn more about how these mouse models have been used in COVID-19 research.

ACE2 Catalog Models - Exclusive Event

As researchers investigate the implications of ACE2 in COVID-19 pathology, different animal models may be needed to explore the mechanisms of ACE2 in its entirety. There are multiple approaches to developing humanized ACE2 (hACE2) models, including ROSA26 conditional knockin (cKI) or endogenous replacement, which yield different proteins. Given the early stages of most ACE2 research performed in animal models, there has yet to be sufficient evidence to determine the explicit advantages of either humanized model generation method.

Despite these challenges, using a variety of animal models can serve to elucidate the function of ACE2 in COVID-19 onset. To support this approach, Cyagen is offering mice from across ACE2 model generation methods and/or strain backgrounds.  Enjoy hACE2 or ACE2 KO models in either C57BL/6J or BALB/c strain backgrounds at special prices.

Additionally, we are excited to be able to provide several technical reports about the progress on these ACE2 models on your request. Learn more about this offer:
 
ACE2 Models - Support your action in fighting COVID-19!

Custom Animal Models for COVID-19 Research

As a leading provider of animal models with a strong basis in social responsibility – Cyagen’s research and development (R&D) team continues to make every effort to help research progress through developing both animal models catered to the global SARS-CoV-2/COVID-19 research initiative. In addition to the above-listed ACE2 models, Cyagen is also prioritizing inquiries on other COVID-19 models, including DPP4 and APN gene targets. Our gene modification experts stand by to assist with developing custom animal models to meet the requirements for your study.