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Scientists have been using mice as models for immunological studies for years, despite scattered evidence that they may not be completely suitable. Now, a new paper published in Nature Communications demonstrates the significant differences between the immune systems of laboratory-raised mice and their wild-caught house cousins.

Most modern studies of mammalian immunity involve using inbred, laboratory-adapted families of house mice, Mus musculus domesticus, as models to observe disease progression. Because of their popularity, most mice used in experiments today have been genetically isolated from wild house mice for more than eight decades and so exhibit a much lower genetic diversity. In the past fears have been raised that this isolation is progressively making the models less and less suitable equivalents for mammals as a whole.

The new study reinforces these concerns. Using 181 wild mice and 64 lab-raised mice, the team characterised the serological, cellular, and functional immune parameters of each group and compared the results.

Generally, the team found that the immune systems of the wild mice were more active, remaining in a highly activated, or ‘primed’ state. They also discovered that wild mice possessed a population of highly activated myeloid cells, which are involved in the immune response, that lab-raised mice did not display. Previous work has shown that primed immune systems are often linked to infections, and the team therefore reasoned that the highly activated states of wild mice were as a result of their higher level of pathogen exposure.

However, the results did also show that wild mice had reduced in vitro cytokine responses to pathogen-associated ligands. While the reasons for this are not clear, the team theorised that it reflected the need to maintain immune homeostasis despite the intense antigenic challenge faced by wild mice.

Other minor differences were also noted by the team, including the increased sex-related differences of lab mice in comparison to wild ones.

“These results point to us having to be much more cautious in extrapolating from the lab to the wild, but laboratory mouse models will continue to be hugely important in biological and biomedical research,” said Mark Viney, Ph.D., co-author of the paper and a Professor in the School of Biological Sciences at the University of Bristol.