Laboratory mice born to wild mice have natural microbiota and model human immune responses
Open accessAbstract
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
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“showed that “wildlings” mice obtained by implanting lab-strain embryos into wild mice had a systemic immune phenotype and a bacterial, viral and fungal microbiome much closer to those of their wild counterparts [58].”
BackgroundBurger, S., Stenger, T., Pierson, M., Sridhar, A., Huggins, M. A., Kucaba, T. A., Griffith, T. S., Hamilton, S. E., & Schuldt, N. J. (2023) · The Journal of Immunology · doi:10.4049/jimmunol.2300061 · Cited by 21 · see citing works
Personalized precision medicine
Konieczny, L., & Roterman, I. (2019) · Bio-Algorithms and Med-Systems · doi:10.1515/bams-2019-0047 · Cited by 9 · see citing works
- Authors
- Rosshart, S. P., Herz, J., Vassallo, B. G., Hunter, A., Wall, M. K., Badger, J. H., McCulloch, J. A., Anastasakis, D. G., Sarshad, A. A., Leonardi, I., Collins, N., Blatter, J. A., Han, S.-J., Tamoutounour, S., Potapova, S., Foster St. Claire, M. B., Yuan, W., Sen, S. K., Dreier, M. S., Hild, B., Hafner, M., Wang, D., Iliev, I. D., Belkaid, Y., Trinchieri, G., & Rehermann, B.
- Affiliations
- National Institutes of Health (US)
- University of Virginia (US)
- United States Department of Health and Human Services (US)
- Weill Cornell Medicine (US)
- Washington University in St. Louis (US)
- Laboratory of Animal Sciences Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, USA.
- Corresponding author
- Rosshart, Stephan P.
- Herz, Jasmin
- Vassallo, Brian G.
- Rehermann, Barbara
- ORCID
- Rosshart, Stephan P.
- Herz, Jasmin
- Vassallo, Brian G.
- Badger, Jonathan H.
- McCulloch, John A.
- Anastasakis, Dimitrios G.
- Sarshad, Aishe A.
- Leonardi, Irina
- Blatter, Joshua A.
- Potapova, Svetlana
- Yuan, Wuxing
- Sen, Shurjo K.
- Dreier, Matthew S.
- Hild, Benedikt
- Hafner, Markus
- Wang, David
- Iliev, Iliyan D.
- Belkaid, Yasmine
- Trinchieri, Giorgio
- Rehermann, Barbara
- Venue
- Science
- Published
- 2019-08-02
- Volume
- 365
- Issue
- 6452
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7377314
- OpenAlex
- W2965604684
- Cited by
- 572
- References
- 68
- Citations by year
- 2026: 53 · 2025: 92 · 2024: 76 · 2023: 81 · 2022: 71 · 2021: 104 · 2020: 74 · 2019: 20
- FWCI
- 22.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DDIR Innovation Award, DK113136, AI137157-01)
- National Cancer Institute (intramural research program)
- National Institute of Allergy and Infectious Diseases (intramural research program)
- National Institute of Diabetes and Digestive and Kidney Diseases (intramural research program)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (intramural research program)
- Crohn’s and Colitis Foundation (Senior Research Award)
- Kenneth Rainin Foundation
- ARC Foundation for Cancer Research
- European Molecular Biology Organization (EMBO) fellowship (ALTF1535-2014)
- Swedish Resarch Council (2015-06376)
- Deutsche Forschungsgemeinschaft (HI 2088/1-1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- embryo transfer, gut microbiota, fungal communities, virome, immune response modeling, translational research, reproducibility, pathogen colonization, natural microbiota
- MeSH terms
- Gastrointestinal Microbiome, Host Microbial Interactions, Animals, Animals, Wild, Humans, Immunity, Mice, Inbred C57BL, Models, Animal, Mice, Host-Pathogen Interactions, Translational Research, Biomedical
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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