A Model System for Feralizing Laboratory Mice in Large Farmyard-Like Pens

Laboratory mice are typically housed under extremely clean laboratory conditions, far removed from the natural lifestyle of a free-living mouse. There is a risk that this isolation from real-life conditions may lead to poor translatability and misinterpretation of results. We and others have shown t...

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Main Authors: Henriette Arnesen, Linn Emilie Knutsen, Bente Wabakken Hognestad, Grethe Marie Johansen, Mats Bemark, Oliver Pabst, Anne Kristine Storset, Preben Boysen
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-01-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2020.615661/full
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author Henriette Arnesen
Henriette Arnesen
Linn Emilie Knutsen
Bente Wabakken Hognestad
Grethe Marie Johansen
Mats Bemark
Mats Bemark
Oliver Pabst
Anne Kristine Storset
Preben Boysen
author_facet Henriette Arnesen
Henriette Arnesen
Linn Emilie Knutsen
Bente Wabakken Hognestad
Grethe Marie Johansen
Mats Bemark
Mats Bemark
Oliver Pabst
Anne Kristine Storset
Preben Boysen
author_sort Henriette Arnesen
collection DOAJ
description Laboratory mice are typically housed under extremely clean laboratory conditions, far removed from the natural lifestyle of a free-living mouse. There is a risk that this isolation from real-life conditions may lead to poor translatability and misinterpretation of results. We and others have shown that feral mice as well as laboratory mice exposed to naturalistic environments harbor a more diverse gut microbiota and display an activated immunological phenotype compared to hygienic laboratory mice. We here describe a naturalistic indoors housing system for mice, representing a farmyard-type habitat typical for house mice. Large open pens were installed with soil and domestic animal feces, creating a highly diverse microbial environment and providing space and complexity allowing for natural behavior. Laboratory C57BL/6 mice were co-housed in this system together with wild-caught feral mice, included as a source of murine microbionts. We found that mice feralized in this manner displayed a gut microbiota structure similar to their feral cohabitants, such as higher relative content of Firmicutes and enrichment of Proteobacteria. Furthermore, the immunophenotype of feralized mice approached that of feral mice, with elevated levels of memory T-cells and late-stage NK cells compared to laboratory-housed control mice, indicating antigenic experience and immune training. The dietary elements presented in the mouse pens could only moderately explain changes in microbial colonization, and none of the immunological changes. In conclusion, this system enables various types of studies using genetically controlled mice on the background of adaptation to a high diversity microbial environment and a lifestyle natural for the species.
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spelling doaj.art-d52e4f153e484959b2366e4de98119e22022-12-21T23:19:39ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-01-011110.3389/fmicb.2020.615661615661A Model System for Feralizing Laboratory Mice in Large Farmyard-Like PensHenriette Arnesen0Henriette Arnesen1Linn Emilie Knutsen2Bente Wabakken Hognestad3Grethe Marie Johansen4Mats Bemark5Mats Bemark6Oliver Pabst7Anne Kristine Storset8Preben Boysen9Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, NorwayFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Aas, NorwayFaculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, NorwayFaculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, NorwayFaculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, NorwayDepartment of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenRegion Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Immunology and Transfusion Medicine, Gothenburg, SwedenInstitute of Molecular Medicine, RWTH Aachen University, Aachen, GermanyFaculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, NorwayFaculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, NorwayLaboratory mice are typically housed under extremely clean laboratory conditions, far removed from the natural lifestyle of a free-living mouse. There is a risk that this isolation from real-life conditions may lead to poor translatability and misinterpretation of results. We and others have shown that feral mice as well as laboratory mice exposed to naturalistic environments harbor a more diverse gut microbiota and display an activated immunological phenotype compared to hygienic laboratory mice. We here describe a naturalistic indoors housing system for mice, representing a farmyard-type habitat typical for house mice. Large open pens were installed with soil and domestic animal feces, creating a highly diverse microbial environment and providing space and complexity allowing for natural behavior. Laboratory C57BL/6 mice were co-housed in this system together with wild-caught feral mice, included as a source of murine microbionts. We found that mice feralized in this manner displayed a gut microbiota structure similar to their feral cohabitants, such as higher relative content of Firmicutes and enrichment of Proteobacteria. Furthermore, the immunophenotype of feralized mice approached that of feral mice, with elevated levels of memory T-cells and late-stage NK cells compared to laboratory-housed control mice, indicating antigenic experience and immune training. The dietary elements presented in the mouse pens could only moderately explain changes in microbial colonization, and none of the immunological changes. In conclusion, this system enables various types of studies using genetically controlled mice on the background of adaptation to a high diversity microbial environment and a lifestyle natural for the species.https://www.frontiersin.org/articles/10.3389/fmicb.2020.615661/fullanimal modelmiceferal miceferalized micetrained immunityimmune experience
spellingShingle Henriette Arnesen
Henriette Arnesen
Linn Emilie Knutsen
Bente Wabakken Hognestad
Grethe Marie Johansen
Mats Bemark
Mats Bemark
Oliver Pabst
Anne Kristine Storset
Preben Boysen
A Model System for Feralizing Laboratory Mice in Large Farmyard-Like Pens
Frontiers in Microbiology
animal model
mice
feral mice
feralized mice
trained immunity
immune experience
title A Model System for Feralizing Laboratory Mice in Large Farmyard-Like Pens
title_full A Model System for Feralizing Laboratory Mice in Large Farmyard-Like Pens
title_fullStr A Model System for Feralizing Laboratory Mice in Large Farmyard-Like Pens
title_full_unstemmed A Model System for Feralizing Laboratory Mice in Large Farmyard-Like Pens
title_short A Model System for Feralizing Laboratory Mice in Large Farmyard-Like Pens
title_sort model system for feralizing laboratory mice in large farmyard like pens
topic animal model
mice
feral mice
feralized mice
trained immunity
immune experience
url https://www.frontiersin.org/articles/10.3389/fmicb.2020.615661/full
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