New model can help translate mice research into human health results

A new mouse model that could improve the translation of research in mice into advances in human health has been developed by researchers at the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

The mouse model, which the scientists called ‘wildling’, acquired the microbes and pathogens of wild mice, while maintaining the laboratory mice’s genetics that make them more useful for research. In two pre-clinical 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, MD, chief of the Immunology Section in NIDDK’s Liver Diseases Branch and 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.”

For this study Rehermann and Stephan Rosshart, MD transplanted embryos of the most commonly used strain of laboratory mice for immune system research into female wild mice, who then gave birth to wildlings. The researchers 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,” added Rosshart. 

They also tested the stability and resilience of the wildlings’ microbiota and found the microbiota was stable across five generations and resilient to environmental challenges. The authors suggest that the stability and resilience of wildlings, if the model is used widely, could improve the validity and reproducibility of biomedical studies.

The researchers also tested how well the wildlings could predict human immune responses. They did this by treating wildlings and lab mice with the same drugs. The wildlings, but not the lab mice, mimicked the human responses seen in clinical trials.

The study was published online in Science.