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

Author:

Rosshart Stephan P.1ORCID,Herz Jasmin2,Vassallo Brian G.1ORCID,Hunter Ashli1,Wall Morgan K.2,Badger Jonathan H.3ORCID,McCulloch John A.3,Anastasakis Dimitrios G.4,Sarshad Aishe A.4,Leonardi Irina5ORCID,Collins Nicholas6,Blatter Joshua A.7ORCID,Han Seong-Ji6,Tamoutounour Samira6,Potapova Svetlana8,Foster St. Claire Mark B.8,Yuan Wuxing39ORCID,Sen Shurjo K.39ORCID,Dreier Matthew S.1,Hild Benedikt1,Hafner Markus4ORCID,Wang David10,Iliev Iliyan D.5ORCID,Belkaid Yasmine6ORCID,Trinchieri Giorgio3ORCID,Rehermann Barbara1ORCID

Affiliation:

1. Immunology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, USA.

2. Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.

3. Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20892, USA.

4. Laboratory of Muscle Stem Cells and Gene Regulation, National Institute for Arthritis and Musculoskeletal and Skin Disease, Bethesda, MD 20892, USA.

5. The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA.

6. Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

7. Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.

8. Laboratory of Animal Sciences Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, USA.

9. Leidos Biomedical Research, Inc., Microbiome and Genetics Core, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

10. Departments of Molecular Microbiology and Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Abstract

Born to be a wildling Inbred laboratory mouse strains are used extensively in basic and translational immunology research. However, the commensal and pathogenic repertoire of resident microbes encountered in the wild is not replicated in a lab setting. This can substantially distort how the immune system develops and functions, leading to false assumptions of how our own “wild” immune system works. Rosshart et al. circumvented this dilemma by implanting lab-strain embryos into wild mice (see the Perspective by Nobs and Elinav). The resultant “wildlings” had a systemic immune phenotype and a bacterial, viral, and fungal microbiome much closer to those of their wild counterparts. In two preclinical experiments, where lab mice had previously failed to predict the human response to drug treatments, wildlings accurately phenocopied patient outcomes. Science , this issue p. eaaw4361 ; see also p. 444

Funder

National Institutes of Health

National Cancer Institute

National Institute of Allergy and Infectious Diseases

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Crohn’s and Colitis Foundation

Kenneth Rainin Foundation

ARC Foundation for Cancer Research

European Molecular Biology Organization (EMBO) fellowship

Swedish Resarch Council

Deutsche Forschungsgemeinschaft

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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