Kamila Karimjee, Rachel C M River, Emil Olsen, Yu-Mei Chang, Dominic J Wells, Monica A Daley, Richard J Piercy
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Long-term, age-associated activity quantification in the DE50-MD dog model of Duchenne muscular dystrophy.
Animal models with a clinically relevant phenotype remain important for robust evaluation of novel therapeutics for the fatal X-linked genetic disorder Duchenne muscular dystrophy (DMD). Demonstration of functional improvement is crucial for both patients and regulatory authorities. Here, we investigate non-invasive methods to quantify activity changes in DE50-MD dogs. Using collar-based Axivity-AX3 tri-axial accelerometers, we measured activity in affected DE50-MD male dogs (3-8 per age point) and littermate wild-type (WT) male controls (3-13 per age point) at monthly intervals from 3 to 18 months of age. Acceleration vector magnitudes were used to derive a series of activity measures over 24 h. Mixed model analyses were used to examine differences between affected and WT groups at different ages. Activity indicators for DE50-MD dogs were significantly higher for percent time spent at rest (P<0.001) and significantly lower for all other activity indicators (all P<0.05), when compared to age-matched WT dogs. Relatively few animals would be required to detect treatment effects with adequate power using these unbiassed, selected and composite activity measures. Our approach reveals opportunities for cross-model standardisation of activity monitoring.
期刊介绍:
Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.