Throughout the history of animal research, mice and rats are the animals that we have used for the longest period of time. They are also the animals that we have standardized the most over time. By some measures, laboratory (hereafter lab) mice have been genetically isolated from their wild cousins for more than 80 years. This means that only a fraction of the genetic variation present in wild mice is present within lab mice.

There are major differences between wild mice and lab mice. These differences can include everything from coat color and average weight to immune phenotype and function. We have intentionally selected for particular qualities in lab mice over time, such as rapid growth, early maturation, high fecundity, and docility. But, we have likely made inadvertent selections for immunological traits along the way too. Also, lab mice typically live in a highly controlled and regulated environment. This includes unlimited access to food and an environment free of many or most pathogens.

What does this mean for animal research and its applicability to humans? Some already question the validity of animal research, and the substantial differences between lab and wild mice highlights another problem: the way that we have bred mice to control for every possible variable means that we understand mice in labs, but know much less about how “the real world” affects these mice. As the authors of this paper state, “comparison of the immune function of wild and laboratory mice is required to reveal both the utility and the limitations of laboratory mice as broadly applicable and relevant immunological models.” The researchers undertook a “detailed phenotypic and functional analysis” of the immune systems of 460 wild mice from 12 different sites in the south of the U.K. The researchers presented their complete data set as a “community resource” for other researchers.

The results point to a wide variety of differences—some significant and some less so—between lab mice and wild mice. Many of the differences concern complex genetics and immunology. More broadly, the study shows that there are some potentially serious methodological concerns regarding animal research. In this case, it is easy to understand why lab mice and wild mice may be vastly different, meaning they show different results in the same experiments. It is this type of simple problem that is excellent to highlight in advocacy.