TY - JOUR
T1 - Laboratory mice born to wild mice have natural microbiota and model human immune responses
AU - Rosshart, Stephan P.
AU - Herz, Jasmin
AU - Vassallo, Brian G.
AU - Hunter, Ashli
AU - Wall, Morgan K.
AU - Badger, Jonathan H.
AU - McCulloch, John A.
AU - Anastasakis, Dimitrios G.
AU - Sarshad, Aishe A.
AU - Leonardi, Irina
AU - Collins, Nicholas
AU - Blatter, Joshua A.
AU - Han, Seong Ji
AU - Tamoutounour, Samira
AU - Potapova, Svetlana
AU - Foster St Claire, Mark B.
AU - Yuan, Wuxing
AU - Sen, Shurjo K.
AU - Dreier, Matthew S.
AU - Hild, Benedikt
AU - Hafner, Markus
AU - Wang, David
AU - Iliev, Iliyan D.
AU - Belkaid, Yasmine
AU - Trinchieri, Giorgio
AU - Rehermann, Barbara
N1 - Funding Information:
This study was supported by the intramural research programs of NIDDK, NCI, NIAMS, and NIAID and the NIH DDIR's Innovation Award. A.A.S. was supported by postdoctoral fellowship 2015-06376 from the Swedish Research Council; I.L. by a Crohn's and Colitis Foundation award; S.T. by European Molecular Biology Organization fellowship ALTF1535-2014 and by the ARC Foundation for Cancer Research; B.H. by research fellowship HI 2088/1-1 from the Deutsche Forschungsgemeinschaft; and I.D.I. by NIH grants DK113136 and AI137157-01, the Kenneth Rainin Foundation, and the Crohn's and Colitis Foundation Senior Research Award.
Publisher Copyright:
© 2019 American Association for the Advancement of Science. All rights reserved.
PY - 2019/8/2
Y1 - 2019/8/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071024951&partnerID=8YFLogxK
U2 - 10.1126/science.aaw4361
DO - 10.1126/science.aaw4361
M3 - Article
C2 - 31371577
AN - SCOPUS:85071024951
SN - 0036-8075
VL - 365
JO - Science
JF - Science
IS - 6452
M1 - 461
ER -