Medical interventions that work well when tested in mouse models can fail when they advance to safety and efficacy testing in humans. One reason for this, scientists propose, may be the differences between immune system development in laboratory mice and humans. Laboratory mice are raised in pathogen-free environments lacking microbial diversity that may contribute to these differences, concludes a new study funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. A scientific team led by Stephen C. Jameson and David Masopust of the University of Minnesota found that co-housing laboratory mice with mice from pet stores can produce “dirty mouse” models that may better reflect the immune systems of adult human beings.
The research team first explored immunological differences between laboratory mice and humans by analyzing cervical tissue specimens from adults of each species. The researchers found that laboratory mice had fewer, less diverse and less widely distributed memory T cells, a type of immune cell, compared with humans. The immune systems of laboratory mice more closely resembled those of human infants, particularly with regard to the number and tissue distribution of memory T cells.
Next the researchers performed a similar analysis on tissues from laboratory mice and from mice found in barn or pet store environments. The non-laboratory mice had immune systems more like those of adult humans, suggesting the variation in microbial environment—and not the species difference—could account for the different immune system makeups.
The researchers then explored if the immune systems of laboratory mice with little exposure to environmental microbes could change when exposed to a different environment. They co-housed laboratory mice with healthy mice raised in a pet store. After eight weeks, analysis of the laboratory mice revealed patterns of T cells and other immune system components that more closely matched the pet store mice as well as adult humans. These findings suggest that “dirty mice” may model the human immune system more closely than typical laboratory mice and could be studied to learn more about the role of environment and genetics in the development of the human immune system.
D Masopust et al. Normalizing the Environment Recapitulates Adult Human Immune Traits in Laboratory Mice. Nature DOI: 10.1038/nature17655 (2016).
Annette Rothermel, Ph.D., program officer in the Autoimmunity and Mucosal Immunology Branch of NIAID’s Division of Allergy, Immunology and Transplantation, is available to comment on the study.