The rearing environment persistently modulates mouse phenotypes from the molecular to the behavioural level.

Jaric, Ivana; Völkl, Bernhard; Clerc, Melanie; Schmid, Marc W; Novak, Janja; Rosso, Marianna; Rufener, Reto; von Kortzfleisch, Vanessa Tabea; Richter, S Helene; Buettner, Manuela; Bleich, André; Amrein, Irmgard; Wolfer, David P; Touma, Chadi; Sunagawa, Shinichi; Würbel, Hanno (2022). The rearing environment persistently modulates mouse phenotypes from the molecular to the behavioural level. PLoS biology, 20(10), e3001837. Public Library of Science 10.1371/journal.pbio.3001837

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The phenotype of an organism results from its genotype and the influence of the environment throughout development. Even when using animals of the same genotype, independent studies may test animals of different phenotypes, resulting in poor replicability due to genotype-by-environment interactions. Thus, genetically defined strains of mice may respond differently to experimental treatments depending on their rearing environment. However, the extent of such phenotypic plasticity and its implications for the replicability of research findings have remained unknown. Here, we examined the extent to which common environmental differences between animal facilities modulate the phenotype of genetically homogeneous (inbred) mice. We conducted a comprehensive multicentre study, whereby inbred C57BL/6J mice from a single breeding cohort were allocated to and reared in 5 different animal facilities throughout early life and adolescence, before being transported to a single test laboratory. We found persistent effects of the rearing facility on the composition and heterogeneity of the gut microbial community. These effects were paralleled by persistent differences in body weight and in the behavioural phenotype of the mice. Furthermore, we show that environmental variation among animal facilities is strong enough to influence epigenetic patterns in neurons at the level of chromatin organisation. We detected changes in chromatin organisation in the regulatory regions of genes involved in nucleosome assembly, neuronal differentiation, synaptic plasticity, and regulation of behaviour. Our findings demonstrate that common environmental differences between animal facilities may produce facility-specific phenotypes, from the molecular to the behavioural level. Furthermore, they highlight an important limitation of inferences from single-laboratory studies and thus argue that study designs should take environmental background into account to increase the robustness and replicability of findings.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Veterinary Public Health Institute
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Veterinary Public Health Institute > Animal Welfare Division

UniBE Contributor:

Jaric, Ivana, Völkl, Bernhard, Novak, Janja, Rosso, Marianna, Würbel, Hanno

Subjects:

600 Technology > 630 Agriculture

ISSN:

1544-9173

Publisher:

Public Library of Science

Language:

English

Submitter:

Pubmed Import

Date Deposited:

24 Oct 2022 13:03

Last Modified:

05 Dec 2022 16:26

Publisher DOI:

10.1371/journal.pbio.3001837

PubMed ID:

36269766

BORIS DOI:

10.48350/173996

URI:

https://boris.unibe.ch/id/eprint/173996

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