Show simple item record

dc.contributor.authorWalker, Men
dc.contributor.authorFureix, Cen
dc.contributor.authorPalme, Ren
dc.contributor.authorNewman, JAen
dc.contributor.authorAhloy Dallaire, Jen
dc.contributor.authorMason, Gen
dc.date.accessioned2017-12-12T18:06:43Z
dc.date.available2017-12-12T18:06:43Z
dc.date.issued2016-01-27en
dc.identifier.urihttp://hdl.handle.net/10026.1/10416
dc.description.abstract

BACKGROUND: Inefficient experimental designs are common in animal-based biomedical research, wasting resources and potentially leading to unreplicable results. Here we illustrate the intrinsic statistical power of split-plot designs, wherein three or more sub-units (e.g. individual subjects) differing in a variable of interest (e.g. genotype) share an experimental unit (e.g. a cage or litter) to which a treatment is applied (e.g. a drug, diet, or cage manipulation). We also empirically validate one example of such a design, mixing different mouse strains -- C57BL/6, DBA/2, and BALB/c -- within cages varying in degree of enrichment. As well as boosting statistical power, no other manipulations are needed for individual identification if co-housed strains are differentially pigmented, so also sparing mice from stressful marking procedures. METHODS: The validation involved housing 240 females from weaning to 5 months of age in single- or mixed- strain trios, in cages allocated to enriched or standard treatments. Mice were screened for a range of 26 commonly-measured behavioural, physiological and haematological variables. RESULTS: Living in mixed-strain trios did not compromise mouse welfare (assessed via corticosterone metabolite output, stereotypic behaviour, signs of aggression, and other variables). It also did not alter the direction or magnitude of any strain- or enrichment-typical difference across the 26 measured variables, or increase variance in the data: indeed variance was significantly decreased by mixed- strain housing. Furthermore, using Monte Carlo simulations to quantify the statistical power benefits of this approach over a conventional design demonstrated that for our effect sizes, the split- plot design would require significantly fewer mice (under half in most cases) to achieve a power of 80%. CONCLUSIONS: Mixed-strain housing allows several strains to be tested at once, and potentially refines traditional marking practices for research mice. Furthermore, it dramatically illustrates the enhanced statistical power of split-plot designs, allowing many fewer animals to be used. More powerful designs can also increase the chances of replicable findings, and increase the ability of small-scale studies to yield significant results. Using mixed-strain housing for female C57BL/6, DBA/2 and BALB/c mice is therefore an effective, efficient way to promote both refinement and the reduction of animal-use in research.

en
dc.format.extent11 - ?en
dc.languageengen
dc.language.isoengen
dc.subjectAge Factorsen
dc.subjectAgingen
dc.subjectAnimal Welfareen
dc.subjectAnimalsen
dc.subjectBehavior, Animalen
dc.subjectBiomedical Researchen
dc.subjectFemaleen
dc.subjectHousing, Animalen
dc.subjectMice, Inbred BALB Cen
dc.subjectMice, Inbred C57BLen
dc.subjectMice, Inbred DBAen
dc.subjectMonte Carlo Methoden
dc.subjectPregnancyen
dc.subjectReproducibility of Resultsen
dc.subjectResearch Designen
dc.subjectSpecies Specificityen
dc.subjectWeaningen
dc.titleMixed-strain housing for female C57BL/6, DBA/2, and BALB/c mice: validating a split-plot design that promotes refinement and reduction.en
dc.typeJournal Article
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/26817696en
plymouth.volume16en
plymouth.publication-statusPublished onlineen
plymouth.journalBMC Med Res Methodolen
dc.identifier.doi10.1186/s12874-016-0113-7en
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/00 Groups by role
plymouth.organisational-group/Plymouth/00 Groups by role/Academics
plymouth.organisational-group/Plymouth/Faculty of Health and Human Sciences
plymouth.organisational-group/Plymouth/Faculty of Health and Human Sciences/School of Psychology
plymouth.organisational-group/Plymouth/Faculty of Science and Engineering
plymouth.organisational-group/Plymouth/Faculty of Science and Engineering/School of Biological and Marine Sciences
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA04 Psychology, Psychiatry and Neuroscience
dc.publisher.placeEnglanden
dcterms.dateAccepted2016-01-19en
dc.identifier.eissn1471-2288en
dc.rights.embargoperiodNot knownen
rioxxterms.versionofrecord10.1186/s12874-016-0113-7en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-01-27en
rioxxterms.typeJournal Article/Reviewen


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record


All items in PEARL are protected by copyright law.
Author manuscripts deposited to comply with open access mandates are made available in accordance with publisher policies. Please cite only the published version using the details provided on the item record or document. In the absence of an open licence (e.g. Creative Commons), permissions for further reuse of content should be sought from the publisher or author.
Theme by 
@mire NV