Towards humane end points: behavioural changes precede clinical signs of disease in a Huntington's disease model

Littin, K.E., Acevedo, A., Browne, W., Edgar, J.L., Mendl, M., Owen, D., Sherwin, C.M., Würbel, H. and Nicol, CJ.
Proceedings of the Royal Society B Biological Sciences, 275:1645, 1865-1874

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 1 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.

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Multivariate response model?
Longitudinal data?
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Paper looks at how changes in behaviour in lab mice can be used as an alternative to more invasive methods when assessing clinical endpoints

Paper submitted by
William Browne, Bristol Veterinary School, University of Bristol,
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