Researchers at the NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) have developed a new mouse model. Called wildlings, the new model has the microbes and pathogens of wild mice, while maintaining the laboratory mice's genetics that make them more useful for research. According to a paper published in Science today, in two preclinical studies, wildlings mirrored human immune responses, where lab mice failed to do so.
"We wanted to create a mouse model that better resembles a mouse you'd find in the wild," said Barbara Rehermann, M.D., senior author on the study. "Our rationale was that the immune responses and microbiota of wild mice and humans are likely shaped in a similar way—through contact with diverse microbes out in the real world."
Rehermann and Stephan Rosshart, M.D., the study's lead author, have long sought to improve animal models of complex diseases in humans. In 2017, they led research showing that transferring wild mice gut microbiota into lab mice helped the mice survive an otherwise lethal flu virus infection and fight colorectal cancer.
In the current study, they transplanted embryos of the most commonly used strain of laboratory mice for immune system research into female wild mice, who then gave birth to and raised wildlings. The researchers and their collaborators compared the microbiota of the wildlings, wild mice, and lab mice. They found that the wildlings acquired the microbes and pathogens of wild mice and closely resembled wild mice in their bacterial microbes present at the gut, skin, and vagina, as well as in the number and kinds of fungi and viruses present.
"A healthy microbiome is important not only for the immune system, but also for digestion, metabolism, even the brain," said Rosshart. "The wildling model could help us better understand what causes diseases, and what can protect us from them, thus benefitting many areas of biomedical research."
Image: Researchers harnessed natural microbiota and pathogens to address shortcomings of current mouse models. Image courtesy of Rosshart et al., Science (2019).