Lab mice make poor models

The sheltered life of a laboratory mouse may make it unsuitable to test immunological responses relevant to humans, according to a study by British scientists that highlights the striking differences in the immune systems captive-born mice compared to their wild counterparts.

Their results, published in Nature Communications, suggest that studies with laboratory mice can show what immune responses are possible, but these are not necessarily the immune responses that will actually occur in the real world.

An immune response observed in a laboratory mouse is “just one example of the myriad immune responses that can be generated by outbred, free-living individuals,” they write. “Considerable caution should therefore be exercised in extrapolating results from laboratory mice to free-living animals and human populations.”

The team, led by biologist Mark Viney of the University of Bristol, compared the immune systems of mice bred for the lab with those of wild mice collected from 12 sites throughout southern England. Differences between the laboratory and wild mice were evident in 57 out of 62 immunological measures.

The immune systems of the wild mice were highly active, most likely because their continuous exposure to high levels of environmental antigens and infection over their lives. While the wild mice seem to be “constantly immunologically multi-tasking”, the authors write, laboratory mice are likely to be responding to a very limited antigenic repertoire.

“A typical laboratory mouse experiment will introduce a single pathogen or antigen … into an immunologically naive animal,” they write. “In contrast, the same pathogen or antigen in a wild mouse would encounter an immune system that is already highly active and responding to many other antigens.”

Laboratory mice are the mainstay of experimental immunology, so the implications of the results may be profound.

“Given that the ultimate purpose of the immune system is to provide protection from external environmental threats,” the authors conclude, “the environment in which the immune system is studied is a priori likely to have profound effects on its response.”