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      Social dominance hierarchy type and rank contribute to phenotypic variation within cages of laboratory mice

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          Abstract

          A tacit assumption in laboratory animal research is that animals housed within the same cage or pen are phenotypically more similar than animals from different cages or pens, due to their shared housing environment. This assumption drives experimental design, randomization schemes, and statistical analysis plans, while neglecting social context. Here, we examined whether a domain of social context—social dominance—accounted for more phenotypic variation in mice than cage-identity. First, we determined that cages of mice could be categorized into one of three dominance hierarchies with varying degrees of dominance behavior between cage-mates, and low levels of agonistic behavior in the home-cage. Most groups formed dynamic hierarchies with unclear ranks, contrasting with recent accounts of stable transitive hierarchies in groups of mice. Next, we measured some phenotypic traits, and found that social dominance (i.e. dominance hierarchy type and degree of dominance behavior) consistently accounted for some phenotypic variation in all outcome measures, while cage-identity accounted for phenotypic variation in some measures but virtually no variation in others. These findings highlight the importance of considering biologically relevant factors, such as social dominance, in experimental designs and statistical plans.

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          Most cited references47

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          The Concept and Definition of Dominance in Animal Behaviour

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            Effects of sex and time of day on metabolism and excretion of corticosterone in urine and feces of mice.

            Non-invasive techniques to monitor stress hormones in small animals like mice offer several advantages and are highly demanded in laboratory as well as in field research. Since knowledge about the species-specific metabolism and excretion of glucocorticoids is essential to develop such a technique, we conducted radiometabolism studies in mice (Mus musculus f. domesticus, strain C57BL/6J). Each mouse was injected intraperitoneally with 740 kBq of 3H-labelled corticosterone and all voided urine and fecal samples were collected for five days. In a first experiment 16 animals (eight of each sex) received the injection at 9 a.m., while eight mice (four of each sex) were injected at 9 p.m. in a second experiment. In both experiments radioactive metabolites were recovered predominantly in the feces, although males excreted significantly higher proportions via the feces (about 73%) than females (about 53%). Peak radioactivity in the urine was detected within about 2h after injection, while in the feces peak concentrations were observed later (depending on the time of injection: about 10h postinjection in experiment 1 and about 4h postinjection in experiment 2, thus proving an effect of the time of day). The number and relative abundance of fecal [3H]corticosterone metabolites was determined by high performance liquid chromatography (HPLC). The HPLC separations revealed that corticosterone was extensively metabolized mainly to more polar substances. Regarding the types of metabolites formed, significant differences were found between males and females, but not between the experiments. Additionally, the immunoreactivity of these metabolites was assessed by screening the HPLC fractions with four enzyme immunoassays (EIA). However, only a newly established EIA for 5alpha-pregnane-3beta,11beta,21-triol-20-one (measuring corticosterone metabolites with a 5alpha-3beta,11beta-diol structure) detected several peaks of radioactive metabolites with high intensity in both sexes, while the other EIAs showed only minor immunoreactivity. Thus, our study for the first time provides substantial information about metabolism and excretion of corticosterone in urine and feces of mice and is the first demonstrating a significant impact of the animals' sex and the time of day. Based on these data it should be possible to monitor adrenocortical activity non-invasively in this species by measuring fecal corticosterone metabolites with the newly developed EIA. Since mice are extensively used in research world-wide, this could open new perspectives in various fields from ecology to behavioral endocrinology. Copyright 2003 Elsevier Science (USA)
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              Finding a dominance order most consistent with a linear hierarchy: a new procedure and review.

              A procedure for ordering a set of individuals into a linear or near-linear dominance hierarchy is presented. Two criteria are used in a prioritized way in reorganizing the dominance matrix to find an order that is most consistent with a linear hierarchy: first, minimization of the numbers of inconsistencies and, second, minimization of the total strength of the inconsistencies. The linear ordering procedure, which involves an iterative algorithm based on a generalized swapping rule, is feasible for matrices of up to 80 individuals. The procedure can be applied to any dominance matrix, since it does not make any assumptions about the form of the probabilities of winning and losing. The only assumption is the existence of a linear or near-linear hierarchy which can be verified by means of a linearity test. A review of existing ranking methods is presented and these are compared with the proposed method. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.
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                Author and article information

                Contributors
                j.a.varholick@gmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                20 September 2019
                20 September 2019
                2019
                : 9
                : 13650
                Affiliations
                [1 ]ISNI 0000 0001 0726 5157, GRID grid.5734.5, Division of Animal Welfare, Veterinary Public Health Institute, , University of Bern, ; Bern, Switzerland
                [2 ]ISNI 0000 0004 1936 8091, GRID grid.15276.37, Department of Biology & UF Genetics Institute, , University of Florida, ; Gainesville, USA
                [3 ]ISNI 0000 0001 2172 9288, GRID grid.5949.1, Department of Behavioural Biology, , University of Münster, ; Münster, Germany
                [4 ]ISNI 0000 0000 9686 6466, GRID grid.6583.8, Department of Biomedical Sciences, , University of Veterinary Medicine, ; Vienna, Austria
                [5 ]ISNI 0000 0001 2179 3554, GRID grid.416992.1, Department of Pharmacology & Neuroscience, , Texas Tech University Health Sciences Center, ; Lubbock, TX USA
                [6 ]ISNI 0000 0001 2179 3554, GRID grid.416992.1, School of Medicine, , Garrison Institute on Aging, Texas Tech University Health Sciences Center, ; Lubbock, TX USA
                [7 ]ISNI 0000 0001 2186 7496, GRID grid.264784.b, Department of Civil, Environmental, and Construction Engineering, , Texas Tech University, ; Lubbock, TX USA
                Author information
                http://orcid.org/0000-0001-9466-3662
                http://orcid.org/0000-0002-2934-3010
                http://orcid.org/0000-0002-3767-2922
                Article
                49612
                10.1038/s41598-019-49612-0
                6754368
                31541122
                809f7e0e-a5cf-466f-b16d-35bc98ac474c
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 13 May 2019
                : 28 August 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/100011199, EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013));
                Award ID: 322576
                Award ID: 322576
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                social behaviour,behavioural methods
                Uncategorized
                social behaviour, behavioural methods

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