Abstract
Fundamental discoveries in many aspects of mammalian physiology have been made using laboratory mice as research models. These studies have been facilitated by the genetic tractability and inbreeding of such mice, the large set of immunological reagents that are available, and the establishment of environmentally controlled, high-throughput facilities. Such facilities typically include barriers to keep the mouse colonies free of pathogens and the frequent re-derivation of the mice severely limits their commensal flora. Because humans have co-evolved with microorganisms and are exposed to a variety of pathogens, a growing community of researchers posits that preclinical disease research can be improved by studying mice in the context of the microbiota and pathogens that they would encounter in the natural world. Here, we provide a perspective of how these different approaches can be combined and integrated to improve existing mouse models to enhance our understanding of disease mechanisms and develop new therapies for humans. We also propose that the term ‘mice with natural microbiota’ is more appropriate for describing these models than existing terms such as ‘dirty mice’.
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Acknowledgements
We thank Dr. Qian Liu, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) for comments. This work was supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH (to B.R.), National Science Foundation grant DEB-2153923 and funds from the State of New Jersey (to A.L.G.), NIH grant R01 AI150600 (to D.M.) and NIH grant R01AI155468 (to S.E.H.).
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B.R. conceptualized the review. B.R. and S.E.H. wrote the main body with additions by A.L.G. and constructive comments from D.M. B.R. prepared the figure. All authors contributed to editing of the manuscript, researching data for the tables and providing references. All authors approved the submitted version of the article.
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B.R. discloses that the National Institute of Diabetes and Digestive and Kidney Diseases granted a license on the WildR mice to Taconic Biosciences and has a Collaborative Research Agreement and Development Award with Genentech. The remaining authors declare no competing interests.
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Rehermann, B., Graham, A.L., Masopust, D. et al. Integrating natural commensals and pathogens into preclinical mouse models. Nat Rev Immunol 25, 385–397 (2025). https://doi.org/10.1038/s41577-024-01108-3
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DOI: https://doi.org/10.1038/s41577-024-01108-3
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