London School of Hygiene & Tropical Medicine

Laboratory mice may not be effective models for studying immune responses to disease, according to a new study published in Nature Communications.

The research team from the London School of Hygiene & Tropical Medicine and the University of Bristol studied the immune systems of 460 wild mice taken from 12 sites in the UK. They then compared them with mice bred in captivity.

They found that these two groups of mice have major differences in their immune make-up. The wild mice had highly activated immune systems, most likely because they are more exposed to infections. The wild mice also tightly control their responses to new infections, probably to prevent immune-mediated disease.

In 62 immunological measures, 57 differed between wild and laboratory mice. Importantly, the researchers showed that wild mice have more highly activated myeloid cells – bone marrow cells that initiate immune responses.

The findings have implications for all aspects of medical and scientific research because laboratory mice underpin studies whose results have a transformative effect on human and animal lives through vaccination and other immune-based therapies.

Study co-author Professor Eleanor Riley from the London School of Hygiene & Tropical Medicine said: “Many of our observations in wild mice are reminiscent of what we see in people who are also exposed to a large number of infections throughout their lives. Whilst laboratory mice are an essential resource for exploring the basic components and wiring of mammalian immune systems, our data suggest that observations in laboratory mice may need to be confirmed in more representative, free-living, populations.”

Professor Mark Viney from the University of Bristol’s School of Biological Sciences and a co-author of the study added: "It's remarkable that despite the enormous number of studies of laboratory mice, ours is the first in-depth study of wild mice immune systems. What this shows is that wild mouse immune systems are working at 'warp-speed' compared with their lab cousins.

"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."

Publication

Stephen Abolins, Elizabeth C. King, Luke Lazarou, Laura Weldon, Louise Hughes, Paul Drescher, John G. Raynes, Julius C. R. Hafalla, Mark E. Viney & Eleanor M. Riley. The comparative immunology of wild and laboratory mice, Mus musculus domesticus. Nature Communications. DOI:10.1038/ncomms14811