“Research with mice has been pivotal for identifying the essential steps in immune cell development and function - including recent well publicized advances in cancer immunotherapy, that all have their roots in research on the mouse immune system,” Stephen Jameson, Ph.D., co-senior author of the study, professor in the Department of Laboratory Medicine and Pathology and member of the Center for Immunology, University of Minnesota, told us.
However, these mice don’t reproduce some important aspects of the adult human immune system. So, in the researchers’ new studies they sought to improve the mouse model’s accuracy by examining the impact that environmental exposure to normal mouse microbes had on the immune response.
“The essential question we asked was whether changing the environment in which we maintain lab mice would affect features of their immune system, such that it better resembled that of adult humans,” explained Jameson.
“Current immunology research stresses the importance of using lab mice that are maintained in “clean” barrier facilities, where the animals are carefully kept away from most of the microbes that would be carried in normal mice,” he added.
However, while this is helpful for understanding the immune system’s development, it does not accurately reflect that of humans, as we are exposed to many types of microbes, some naturally occurring and some infectious.
For these reasons, the researchers wanted to examine how a “more normal” immunological environment for the lab mice might improve their similarity to human’s immune systems – thus “dirty mice” instead of artificially clean.
And the researchers’ hypothesis was correct. According to Jameson, the study revealed that the lab mouse’s immune system different from adult humans in “many and varied ways,” but the immune system of wild mice, pet store mice, and co-housed lab mice were much more suited as a model of immune characteristics in adult humans.
In fact, lab mice are a better model for that of new born humans, which Jameson explained is “a useful feature, but of limited value for modeling immune responses for most of a human’s lifetime.”
Additionally, it was found that the changes in the immune system due to natural exposure to mouse microbes led to significant changes in the animal’s capacity to mount a new immune response.
“For example, when these mice were experimentally infected with bacteria, the animals raised in a more normal environment controlled the bacterial infection around 1000-times better than genetically identical animals that are raised in typical lab conditions,” said Jameson.
Creating better therapeutics
As Jameson explained, there have been concerns surrounding the use of laboratory mice to predict humans’ response to therapeutics, and while some, including those involved in cancer immunotherapy, resulted from research with mice, the model has its limitations.
“The new approach we have pioneered generates mice that have immune system characteristics much more like that of adult humans, so we believe this will form a more valuable platform to explore the efficacy of drugs designed to regulate the immune response,” said Jameson.
“An advantage of our system is that we can continue to harness the tremendous power of mouse genetics in our studies, but to make the immune system in these laboratory mice better mirror that of humans.”