title: Towards humane end points: behavioural changes precede clinical signs of disease in a Huntington's disease model.
abstract: The number of animals used in science is increasing, bringing a concomitant obligation to minimize suffering. For animals with progressive conditions, euthanasia at a 'humane end point' is advised if the end point is scientifically valid, predictive and accurate. Our aim was to test the hypothesis that behavioural changes would reliably precede clinical signs of disease in a progressive neurological model, using retrospective analysis. We observed 100 pair-housed female R6/1 transgenic Huntington's disease (HD) mice and 28 pair-housed female wild-type (WT) mice in standard- or resource-enriched cages. Disease progression was monitored until one member of each HD pair reached a pre-defined end point based on pathological symptoms (HD end). This mouse was then euthanized together with its cage mate (HD other) and any matched WT pairs. At euthanasia, HD mice had significantly greater absolute and relative organ weights, and significantly higher alpha1 acid glycoprotein concentrations than WT mice, indicating reduced welfare. HD mice initially showed significantly greater use of cage resources than WT mice but this declined progressively. Steeper declines, and earlier cessation, in the use of some climbing and exploration resources occurred in the HD end mice compared with the HD other mice. Behavioural change can be an early indicator of disease onset.
authors.affiliation: Animal Welfare Group, Ministry of Agriculture and Forestry, PO Box 2526, Wellington, New Zealand.
authors.forename: Kate
authors.initials: K
authors.lastname: Littin
authors.forename: Abraham
authors.initials: A
authors.lastname: Acevedo
authors.forename: William
authors.initials: W
authors.lastname: Browne
authors.forename: Joanne
authors.initials: J
authors.lastname: Edgar
authors.forename: Mike
authors.initials: M
authors.lastname: Mendl
authors.forename: Diane
authors.initials: D
authors.lastname: Owen
authors.forename: Chris
authors.initials: C
authors.lastname: Sherwin
authors.forename: Hanno
authors.initials: H
authors.lastname: Würbel
authors.forename: Christine
authors.initials: C
authors.lastname: Nicol
mesh_terms: D000827:Animal Welfare; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D037901:Euthanasia, Animal; D005260:Female; D006816:Huntington Disease / Q000503:physiopathology / Q000523:psychology*; D008297:Male; D051379:Mice / Q000523:psychology*; D008822:Mice, Transgenic; D012189:Retrospective Studies