Also: Amyotrophic Lateral Sclerosis & Gait in Mice in JNER.
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Gait Dynamics in Mice
Ajit Kale*, Hangyul Chung*, Leonardo Hochberg*,
Ruediger Volk, Jose M. Otero, Ivo Amende, and Thomas G. Hampton.
Mouse Specifics, Inc. and *The CuraVita Corporation, Boston, MA. USA.
Web Published: December 1, 2001
Abstract
In vivo detection of neuromuscular defects in rodents has been limited to the wire-grip or rotarod tests. Gait measurements are usually limited to the stride length metered between inked paw prints. We sought to develop a standardized assay for comprehensive characterization of gait dynamics in mice. Accordingly, paw placements were monitored in 6 adult male mice walking at a speed of 20 cm/s. Swing time was significantly longer in forelimbs compared to hindlimbs (P<0.05). The percentage of stride engaged in stance is significantly longer in hindlimbs. This system and these observations provide a framework for more quantitative evaluation of mouse models of neuromuscular disease.
Methods
Figure 1.
Male B6SJL mice (n=6, age 8-10weeks) were obtained from The Jackson Laboratory. Mice were monitored using the The CuraVita TM Gait Imaging system. Neither anesthetic nor surgery was required. Images from each mouse were acquired through a minimum of 6 complete strides, with all mice ambulating at a speed of 20 cm/s. e-MOUSETM algorithms were used to interpret the waveforms generated by plotting paw placement throughout the gait cycle.1 Swing time, stance time, and the percentages of stride engaged in either the stance (Stance %) or swing (Swing %) phases were determined.
Results
Front vs. Rear Gait Dynamics
Front Limbs (n=6)
Hind Limbs (n=6)
Stance (ms)
297 ± 11
275 ± 9
Swing (ms)
76 ± 9
59 ± 4*
Stance (%)
79 ± 2
83 ± 1*
Swing (%)
21 ± 2
17 ± 1*
*P < 0.05 via Student's 2-tail paired
t-test.
Discussion
What are the early symptoms of neurodegenerative disease or the effects of CNS-active drugs on coordinated movement? What is the physiology of fatigue in amyotrophic lateral sclerosis (ALS)? With support from the ALS Association and The Jackson Laboratory, we are completing development of a robust system to rapidly and non-invasively characterize gait dynamics in mice to accelerate understanding and treatment of neuromuscular diseases. Our CuraVitaTM gait imaging system is capable of screening thousands of mice yearly, without requiring the inking of paws, and provides significantly more information than simply stride length or speed. Data in healthy mice indicate that the load-bearing portion of stance is longer in the hindlimbs compared to the forelimbs. This corresponds to the larger role for weight bearing in the hindlimbs.2 Data obtained from our system, in which ambulatory speed can be pre-set to normalize for walking speeds which may be depressed due to disease, are consistent with previous reports of gait indices in mice.3 Future efforts will result in a standardized high-throughput assay. It will be interesting to explore how gait indices in mouse models of ALS compare to those in patients 4 and research the efficacy of therapies for treating movement disorders5 and neuromuscular diseases. 6
References
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