What are humanized mice? Wait, what?

July 1st 2022

If you are a follower of Speaking of Research (SR), you would probably know from our animal use statistics pages that rodents are the most widely used animal research model.

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Rodents are prevalently used in research because they share approximately 85% of the genes that code for proteins with humans. Proteins are one of the three primary molecules which regulate major functions within the body (the other two are carbohydrates and fats). Despite significant similarity in genomes, mice do not share all of the same genes with humans. This becomes important when considering whether the mouse might be an appropriate model for a disease—enter the humanized mouse. As highlighted by our colleagues at the Foundation for Biomedical Research (FBR), a humanized mouse is simply a mouse that has been genetically modified so that it contains a human gene or human immune cells.

Why is this important? Well, consider the COVID-19 pandemic. We were able to create a vaccine and evaluate its safety and efficacy within a year! Those opposed to animal research would have you believe that this means that animal research is not needed (because the traditional vaccine pipeline is usually a decade or more). So how did we accomplish this? Well, one key reason was the creation of the humanized mouse (containing the human ACE2 gene) in 2007. During the SARS and MERS outbreaks, researchers were extremely worried about a global pandemic. They began studying the SARS and MERS viruses (which belong to the same family of coronaviruses as COVID-19). They realized that the human versions of the ACE2 gene was necessary for infection with these viruses to occur. Mice do have their own version of this gene but it is structurally different from humans, and it is a key reason why humans can get infected, but mice cannot. And so, researchers created a mouse with the human version of that gene (K18-hACE2). 

The K18-hACE2 mouse model is called a transgenic mouse because its genome has been altered and it is also a humanized mouse because it contains a gene that is present in humans.

Mice with the human version of ACE2 become infected with coronaviruses such as SARS, MERS and COVID-19—similarly to humans. The creation of this model allowed for the evaluation of these diseases as well as the formulation of therapeutic strategies, such as vaccines.

Did you know that during the SARS outbreak in 2002, a vaccine was being developed using the humanized mouse model described above? This vaccine was abandoned after the SARS outbreak came to an end, but is a primary reason why we were able to make significant strides within 3 months of the declaration of the COVID-19 pandemic.

As highlighted by our colleagues at FBR, humanized mice are used to treat a host of diseases from Addiction to Dementias to Cancer, to name a few! To learn more about the benefits of animal research check out their website as well as our blog.