Mice, the most commonly used laboratory animals in medical research, may be poor models for studying trauma or infections in humans, scientists found.
In a test comparing the genetic responses of mouse and human immune cells, mouse models had vastly different reactions to toxins and trauma, according to findings published yesterday in the journal Proceedings of the National Academy of Sciences. The results are a reminder that mouse models don’t reflect the intricacy of human ailments, researchers said.
“Studying disease in patients is much more complex than studying model systems,” the authors, led by Ronald Davis, of Stanford University’s Genome Technology Center, wrote. “There are multiple considerations to our finding that transcriptional response in mouse models reflects human diseases so poorly, including the evolutional distance between mice and humans.”
The genetic responses of white blood cells from 167 burn and trauma patients were compared with the reactions of corresponding mouse models in the study from Davis, Ronald Tompkins, a burn specialist at the Massachusetts General Hospital and professor of surgery at Harvard Medical School, and Wenzhong Xiao, who is affiliated with Stanford and Harvard. They found that some genetic responses in humans, which are highly similar between patients, weren’t close to the model mice.
Mice are often used as model organisms for drug testing, to make sure compounds are safe and effective before they go into humans, the authors wrote. However, mice are particularly bad for testing compounds that may change how people’s bodies respond to trauma, burns, and some toxins, like those released by the E. coli bacteria.
Other explanations for the discrepancy may be that the model mice are too inbred to be useful, or that the modeling doesn’t reflect the illnesses experienced by trauma patients. Additionally, the difference in recovery time between mice and people may play a role, and clinical care, such as drugs, surgery and life support, may further attenuate similarities.
The people in the study with trauma injuries were mostly 25 years to 44 years old and severely injured. The median patient had received 1.9 liters of blood in transfusion. About 96 percent of the people survived.
The burn patients had a median of 53 percent of the body covered in burns, although that varied widely, the authors wrote. Just 85 percent of these people survived. Despite these differences, the genes of the white blood cells in the burn and the trauma patients responded similarly to injury, in contrast to those in the mice.
The authors suggest using genetic descriptions of these diseases to create more-similar models.
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