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Science. 2019 Aug 2;365(6452). pii: eaaw4361. doi: 10.1126/science.aaw4361. Epub 2019 Aug 1.

Laboratory mice born to wild mice have natural microbiota and model human immune responses.

Author information

1
Immunology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, USA. stephan.rosshart@uniklinik-freiburg.de rehermann@nih.gov.
2
Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
3
Immunology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, USA.
4
Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20892, USA.
5
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute for Arthritis and Musculoskeletal and Skin Disease, Bethesda, MD 20892, USA.
6
The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA.
7
Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
8
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
9
Laboratory of Animal Sciences Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, USA.
10
Leidos Biomedical Research, Inc., Microbiome and Genetics Core, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
11
Departments of Molecular Microbiology and Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
#
Contributed equally

Abstract

Laboratory mouse studies are paramount for understanding basic biological phenomena but also have limitations. These include conflicting results caused by divergent microbiota and limited translational research value. To address both shortcomings, we transferred C57BL/6 embryos into wild mice, creating "wildlings." These mice have a natural microbiota and pathogens at all body sites and the tractable genetics of C57BL/6 mice. The bacterial microbiome, mycobiome, and virome of wildlings affect the immune landscape of multiple organs. Their gut microbiota outcompete laboratory microbiota and demonstrate resilience to environmental challenges. Wildlings, but not conventional laboratory mice, phenocopied human immune responses in two preclinical studies. A combined natural microbiota- and pathogen-based model may enhance the reproducibility of biomedical studies and increase the bench-to-bedside safety and success of immunological studies.

Comment in

PMID:
31371577
DOI:
10.1126/science.aaw4361

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