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Some mice have crummy immune systems, especially the ones we rely on to learn about our own health. When they’re bred in sterile environments and cut off from the real world, how is that supposed to teach us anything about real humans in the real world? But some researchers argue that wild mice can bridge that gap. A wild mouse’s immune system has way more in common with our own than those of lab mice do, and it could be a huge game changer in modern medicine.
More research is conducted in lab mice than any other animal because scientists know what they’re getting into when they study lab mice, from their genetic makeup to what in the environment is likely to throw them off. But over years of mice being optimized for answering research questions rather than for maintaining their own health, the poor little guys have become really inbred. To keep their genomes totally uniform, researchers may breed the same animals with their siblings for 27 generations at a time.
And researchers like it that way, because it means they’re less likely to accidentally attribute an experimental outcome to the wrong source. For example, if you feel funny after eating a peanut butter sandwich, it could have been because you developed a nut allergy, or it could have been the sushi you ate earlier in the day. Or it could have been the medication you took with the sandwich, or any number of factors that you might not be able to narrow down because you’re exposed to so many new things every day. But the lab mouse eats the same thing for every meal of every day in the same room and hasn’t been exposed to peanut allergens or bad sushi. So if a lab mouse is looking a little low after getting an immunotherapy drug, it was probably because of the drug.
And that’s why research is still conducted in animals. Mice have organs and blood and hormones that serve bigger roles in the living animal than a scientist could observe in a section of tissue. By looking at a tumor cell culture under the microscope, you could learn a lot about its uncontrolled reproduction. But you wouldn’t be able to see how it travels to other parts of the body and spreads cancer. So whole lab mice help scientists develop therapies for whole people.
But researchers are learning that in one area, these lab mice don’t really resemble humans. It’s their immune systems. Despite all of the lab mouse research to find cures for human immune disorders, wild mice have more human-like immune responses. It’s the very qualities that make lab mice so appealing for research that also make them less relevant to solving our problems.
To bridge that gap, some researchers started studying animals that resemble us more closely. We can still use all of the incredible discoveries that have been made over years of lab mouse research by comparing them to a wild relative. Now, compared to inbred, sterile lab mice, pretty much every mouse is wild. When researchers describe wild mice in their experiments, they can range from pet shop mice to those found in the wild. These wild mice differ from lab mice in that they have genetic variation between individuals, which lab mice do not. Additionally, wild mice use their genes differently than lab mice, as they are only activated when encountering a threat. In a study published in 2016, scientists exposed a group of lab mice to various viruses, and they found that the lab mice had an inexperienced immune system compared to the wild mice. The lab mice adapted and began to show genes that had been previously hidden away.
In order to make lab mouse experiments more relevant to those of us living in non-sterile environments, researchers are now breeding lab mice with wild mice as part of the Collaborative Cross initiative. This new, more diverse group of mouse breeds allows researchers to have reproducible results, while also including more representative genetic variation. This has already led to more human-like results, such as the gene Foxp3 which keeps the immune system from fighting itself. We wouldn’t have known about the different amounts of Foxp3 in Collaborative Cross mice compared to inbred mice without a study published in 2017. This was the first stepping stone in bridging the gap between mice and humans. The next step was Diversity Outbred mice, which are the offspring of the Collaborative Cross founding mice. This larger, more representative sample helped researchers identify a gene related to tumor suppression in pancreatic cancer.
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