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Alternatives to Laboratory Animals - ATLA

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Non-invasive Physiology in Conscious Mice

Ajit Kale1 Ivo Amende, Katrina Piskorski, Victor Chu, Jose M. Otero, Peter Mueller and Thomas G. Hampton

Linking gene defect to disease phenotypes in mice has become an essential step in the development of new drugs. Yet, many in vitro and in vivo assays require anaesthetic and surgery or do not reflect physiologically relevant phenomena. The effects of genes or diseases may only become apparent with stressors. Here, we apply non-invasive ECG monitoring and gait imaging systems to describe changes in the electrocardiogram and in gait dynamics resulting from a doubling of the ambulatory speed of mice. We found that B6C3H mice (n = 5) take 3.6 ± 0.1 strides/second to walk 18cm/second and have a heart rate of 750 ± 2bpm after 1 minute of walking at this speed. These mice significantly increase stride frequency to 5.2 ± 0.1 strides/second in order to increase their speed to 36cm/second. The heart rate increased significantly (814 ± 9bpm, p < 0.05) after trotting at the higher speed for 90 seconds, and the QRS interval duration significantly decreased (9.4 ± 0.3ms vs. 10.4 ± 0.3ms, p < 0.05). We discuss the application of the ECG screening and gait imaging systems to mouse models of Duchenne muscular dystrophy, Down syndrome and amyotrophic lateral sclerosis, diseases in humans that are known to affect the heart and neuromuscular systems.