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Of Mice and Men: The importance of Mouse Models in Research

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Laura Tabellini Pierre on February 8, 2021

Many animals share common biology with humans, are affected by similar diseases, and may have a comparable response to certain treatments. Animal models are thus useful to address scientific questions ranging from basic science to the development of vaccines and therapeutics.

The characteristics necessary for a reliable and informative animal model were described in 1987 by M. K. Davidson (1). Requirements sought after are the appropriateness of the model, transferability of information, genetic consistency, universality of results, ease of adaptability to experimental manipulation, and cost/availability. The mouse as an animal model fits these qualifications and has been used in medical research since the early 1900s. (2). Moreover, small animal model systems such as the mouse model serve as high-throughput models for preclinical evaluation to identify highly performing therapies and vaccines.

Mouse models in cancer research have enabled scientists to unravel the whims of tumor biology in dynamic systems, an advantage that experiments with cell culture cannot provide. Cancer mouse models were pivotal in laying the foundation for immuno-oncology by providing information on the crosstalk between cancer and the immune system that revealed the basis of immune evasion, an essential feature for tumor cells survival.

NanoString has an extensive and curated portfolio of customizable nCounter® gene expression panels targeting both human and mouse samples, spanning from oncology to immunology and infectious disease to neuroscience. Our customers have used these panels to investigate various aspects of tumor cell biology such as crosstalk within the tumor microenvironment (TME) or the effects of altered metabolism on the immune response to cancer, as in a recent study on the association of obesity with diminished efficacy of anti-PD-1-based therapies in renal cancer (3). Another paper used the nCounter platform to study the effects of dendritic cell (DC) vaccination and CD40-agonist combination therapy in T cell-dependent antitumor immunity in pancreatic carcinoma (4). The researchers monitored tumor progression and immune responses in the TME and lymphoid organs using the nCounter PanCancer IO 360™ Panel, observing delayed tumor outgrowth after administration of a prophylactic vaccine.

Speaking of vaccines, the COVID-19 pandemic has once more shown the importance of animal models in vaccine development. To this end, scientists immediately started studying the SARS-CoV-2 virus and the disease it causes. In 2020, the Global Mouse Models for COVID-19 Consortium or GMMCC was established to support and enhance “the delivery of relevant mouse strains, mouse genetics expertise, and robust outcome and therapeutic effect and safety testing platforms.” (5).

Mice are not naturally susceptible to SARS-CoV-2, thanks to a difference in their ACE2 protein, the cell surface protein that binds to the coronavirus spike protein; therefore, mice have to be genetically engineered with the human ACE2 (hACE2) receptor in order to be used to study COVID-19.

According to a review paper published last year by Gurumurthy and colleagues, more than two dozen designs may be useful for SARS-CoV-2 research among the three broad categories of mouse models: besides the aforementioned genetically engineered mouse model (GEMM), some researchers have evolutionarily adapted the coronavirus to infect mice by serial passage through mice in order to trigger the emergence of infectious mutant strains.  Another approach is the introduction of hACE2-encoding DNA through adenovirus vector systems followed by infection of the mice with the earlier coronavirus SARS-CoV. While this approach didn’t prove ideal for studying COVID-19 disease—as it didn’t result in lethality—it seems useful for testing vaccine efficacy (6).

Kenneth H. Dinnon III and colleagues went beyond a simple GEMM and remodeled the SARS-CoV-2 S receptor-binding domain to facilitate efficient binding to the mouse ACE2 receptor. With this approach, the group measured the effects of age on COVID-19 in mice as well as the efficacy of both IFN-a treatment and a vaccine delivered via a vector (7).

In 2020, NanoString launched a Human version of the pathogen-agnostic nCounter Host Response Panel to study the phases and progression of infection across the five major components of the host response to infectious agents: Host Susceptibility, Interferon Response, Innate Immune Cell Activation, Adaptive Immune Response, and Homeostasis.

As preclinical studies using mouse models are important for vaccine and therapy development for infectious disease, and given the importance of mouse models for COVID-19, NanoString has now launched a mouse version of the Host Response Panel, with ostensibly the same gene content as the Human version.  The panel is still customizable with the Coronavirus Panel Plus, a 20-gene off-the-shelf spike-in that covers the entire SARS-CoV-2 genome and additional coronavirus family genes, plus the Human ACE2 receptor.  You can add an entirely custom Panel Plus of up to 55 genes to either the Human or Mouse Host Response Panel – check out genes associated with various human and mouse tissues to study the effect of infectious disease on various organs by having a look at the Human or Mouse Host Response Tissue Gene Lists.

And, as always, all nCounter gene expression panels come with an easy-to-use, reverse transcription- and amplification-free automated workflow for producing robust and reproducible data.

For Research Use Only. Not for use in diagnostic procedures

(1)https://pubmed.ncbi.nlm.nih.gov/3312096/

(2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484632/

(3) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757487/

(4) https://pubmed.ncbi.nlm.nih.gov/32690771/

(5) https://mousecovid.org/

(6) https://www.nature.com/articles/s41596-020-00403-2 (7) https://www.nature.com/articles/s41586-020-2708-8

Post by Laura Tabellini Pierre