Non-invasive physiology in conscious mice
Ajit Kale1, Ivo Amende, Katrina Piskorski
1The CuraVita Corporation, Boston, MA, USA.
Abstract:
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.
Insights
Non-invasive ECG and gait analysis reveal physiological changes in mice under stress. These methods can aid drug development for heart and neuromuscular diseases in mouse models.
Area of Science:
- Physiology
- Biomedical Engineering
- Animal Models
Background:
- Linking gene defects to disease phenotypes in mice is crucial for drug development.
- Current assays often require anesthesia and surgery, or lack physiological relevance.
- Gene or disease effects may only manifest under stress.
Purpose of the Study:
- To apply non-invasive electrocardiogram (ECG) monitoring and gait imaging systems.
- To describe changes in ECG and gait dynamics in mice at doubled ambulatory speed.
- To assess the utility of these systems for disease modeling.
Main Methods:
- Utilized non-invasive ECG monitoring and gait imaging systems.
- Assessed B6C3H mice (n=5) at walking (18cm/s) and trotting (36cm/s) speeds.
- Monitored heart rate, stride frequency, and QRS interval duration.
Main Results:
- At 36cm/s, stride frequency increased to 5.2 ± 0.1 strides/second.
- Heart rate significantly increased to 814 ± 9 bpm after 90 seconds of trotting (p < 0.05).
- QRS interval duration significantly decreased (9.4 ± 0.3ms vs. 10.4 ± 0.3ms, p < 0.05).
Conclusions:
- Non-invasive ECG and gait analysis can detect physiological changes under stress in mice.
- These systems offer a physiologically relevant alternative to traditional assays.
- Potential applications include mouse models of Duchenne muscular dystrophy, Down syndrome, and amyotrophic lateral sclerosis.
