By housing laboratory mice in hygienic and specific pathogen free barrier facilities, scientists can tightly control conditions for studying immune system function and disease. However, owing to recent failures in translating findings from mouse models to the clinic, there are growing concerns that mice might not be an appropriate species for modeling human disease. In a recent report, a group led by Stephen Jameson and David Masopust at the University of Minnesota show that, rather than blaming the mice, scientists should start taking into account their facility's housing conditions (Nature 532, 512–516; 2016).

The study's goal was to compare the immune systems of laboratory mice with those of humans, to determine what effects standard barrier facility housing conditions might have on translating mouse models to adult humans. According to Jameson, “Standard lab mice don't reflect important features of the adult human immune system. We wanted to know whether this is because lab animals are shielded from microbes that normal mice encounter in the wild.” In their experiments, the researchers focused on studying the composition of memory T cells, which are critical for adaptive immune responses to infections and cancer.

Credit: CreativeNature_nl_iStock_Thinkstock

The group compared the immune systems of human newborns and adults with those of 'clean' laboratory mice and wild-caught or 'dirty' pet-store mice. Unlike the human adult immune system—but similar to that of human newborns— lab mice lacked effector-differentiated and mucosally distributed T cells. To determine if this trend in lab mice was due to a lack of challenge by typical environmental microbes, the research group tested T cell types in wild-caught feral mice and pet-store mice. They found that the immune systems of both wild-caught and pet-store mice had significantly higher levels of effector-differentiated T cells, a signature of the human adult immune system. They further demonstrated that, after adding pet-store mice into the cages of lab mice, the immune systems of clean lab mice began to look less like those of human newborns, and more like those of human adults.

Overall, the results demonstrate the importance of the environment in shaping the makeup and function of the immune system. They also highlight that tight control over lab and vivarium conditions comes with a translational price tag. As said by Masopust, “Utilizing this ['dirty'] model to test vaccinations and therapeutics for cancer or transplantation may better predict how these will perform in humans.”