Low-Cost Gait Analysis for Behavioral Phenotyping of Mouse Models of Neuromuscular Disease

Abstract

Measurement of animal locomotion is a common behavioral tool used to describe the phenotype of a given disease, injury, or drug model. The low-cost method of gait analysis demonstrated here is a simple but effective measure of gait abnormalities in murine models. Footprints are analyzed by painting a mouse's feet with non-toxic washable paint and allowing the subject to walk through a tunnel on a sheet of paper. The design of the testing tunnel takes advantage of natural mouse behavior and their affinity for small dark places. The stride length, stride width, and toe spread of each mouse is easily measured using a ruler and a pencil. This is a well-established and reliable method, and it generates several metrics that are analogous to digital systems. This approach is sensitive enough to detect changes in stride early in phenotype presentation, and due to its non-invasive approach, it allows for testing of groups across life-span or phenotypic presentation.

Figures

Figure 1:. Gait Analysis Measures and Troubleshooting.

A. Schematic representation of gait analysis on mice, depicting stride length, stride width, and toe spread information. B. Representative example of a gait analysis footprint sequence that can be scored, depicting measurement of all three parameters. C. Representative examples of problematic gait analysis footprint sequences that cannot be scored.

Figure 2:. SBMA BAC fxAR121 transgenic mice exhibit a progressive, neurodegenerative gait phenotype that can be detected via gait analysis.

A. Despite no differences at pre-symptomatic ages (2.5 months, nctl=11, nexpt=12), BAC fxAR121 mice develop significantly reduced stride length compared to their non-transgenic littermate controls at post-symptomatic stages (9 months, nctl=8, nexpt=12). B. No changes were detected in stride width at either age. C. Symptomatic SBMA BAC fxAR121 transgenic mice display significantly reduced hind limb toe spread compared to non-transgenic littermate controls. N= 8-12/group. ANOVA with post-hoc Tukey test * p < 0.05, ** p < 0.01. Error bars represent SEM.