Why Researchers Are Making Mice a Little More Human

By Ross Pomeroy - RCP Staff
April 28, 2020
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Mice are not humans. This obvious truth, coupled with issues like poor methodology, reporting bias, and sloppy statistics, explains why – historically – studies conducted on mice have rarely translated to us.

Those latter problems always seem to plague scientific research, no matter how hard scientists try to weed them out. Perhaps that's why in the early 2000s, researchers began working in earnest to re-engineer laboratory mice altogether. The goal? Make them a little more human.

"Humanized models – mice expressing human transgenes or engrafted with functional human cells or tissues – can provide important tools to bridge the gap between animals and humans in preclinical research," wrote Monica J. Justice, Program Head and Senior Scientist in Genetics and Genome Biology at The Hospital for Sick Children.

Mice and humans share roughly 97.5% of their DNA, so one might think that would make us near perfect stand-ins for each other when it comes to studying pharmaceutical treatments and modeling disease. However, the slight difference in our biological coding means that mice are not susceptible to various infections like HIV, Epstein Barr Virus, or Ebola. Moreover, they metabolize drug compounds much differently.

Many of these differences have been quashed in the past couple decades with the proliferation of humanized mice. The key advance was engineering a mouse with a mutation in the Interleukin-2 receptor (IL2). IL2 is a molecule that regulates the activities of white blood cells. Without it, our immune cells are blind. This meant that scientists could graft human cells, tumors, tissues, and even basic immune systems into mice without the animals' own immune systems rejecting them. Humanized mice are susceptible to HIV, Ebola, and even tuberculosis, and their immune systems can be designed to be essentially human.

"These improved humanized mouse models are now being used to study many human biological responses and diseases and are increasingly employed as preclinical tools for evaluation of drugs and for identifying underlying mechanisms in a broad array of diseases," researchers at the University of Massachusetts Medical School wrote in the 2017 review. "Moreover, humanized mice are being increasingly utilized as translational models in many additional areas of biomedical research including regenerative medicine, transplantation, and immunity."

Humanized mice are growing particularly useful for exploring immunotherapy treatments against various cancers.

"The humanized mouse model will permit not only the discovery of effective immunotherapy treatments, but it can be used to predict patient responses to great clinical benefit," a trio of oncologists from the University of Colorado recently opined in the journal Molecular Carcinogenesis.

Any study conducted in animals will always provide an imperfect approximation to what happens in humans, but the rise of the humanized mouse increasingly means that mouse studies are growing more meaningful.

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