期刊
SCIENCE
卷 365, 期 6452, 页码 461-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaw4361
关键词
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资金
- NIDDK
- NCI
- NIAMS
- NIAID
- NIH DDIR's Innovation Award
- Swedish Research Council [2015-06376]
- Crohn's and Colitis Foundation
- European Molecular Biology Organization [ALTF1535-2014]
- ARC Foundation for Cancer Research
- Deutsche Forschungsgemeinschaft [HI 2088/1-1]
- NIH [DK113136, AI137157-01]
- Kenneth Rainin Foundation
- Crohn's and Colitis Foundation Senior Research Award
- Vinnova [2015-06376] Funding Source: Vinnova
- Swedish Research Council [2015-06376] Funding Source: Swedish Research Council
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI001115, ZICAI001233] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [ZIADK054508] Funding Source: NIH RePORTER
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.
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