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Updated: Jun 4, 2025
Low-Cost Gait Analysis for Behavioral Phenotyping of Mouse Models of Neuromuscular Disease
Published on: July 18, 2019
X-Ray Fluoroscopy-Based Kinematic Analysis of Quadrupedal Locomotion in Slow and Fast Fatigue-Resistant Motor
Ayumu Ono1, Daijiro Inomata2, Lisa Ohgaki2
1Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa, Japan.
Introduction/Aims:
VAChT-Cre is a transgenic mouse line targeting slow-twitch fatigue-resistant and fast-twitch fatigue-resistant motor neurons that innervate oxidative type I and type IIa muscle fibers. To ablate these neurons, VAChT-Cre mice were crossbred with NSE-DTA mice, leading to the expression of diphtheria toxin A after Cre-mediated excision. The resulting VAChT-Cre;NSE-DTA mice exhibited motor deficits, abnormal locomotion, muscular atrophy, and tremor, making them a useful model for studying motor neuron physiology and pathology. In this study, we conducted a kinematic analysis to examine their abnormal locomotor phenotype.
Methods:
The quadrupedal walking of VAChT-Cre;NSE-DTA and control mice along a 500 mm acrylic tunnel was analyzed using an X-ray fluoroscopic system. Stride duration, stride length, footfall patterns, and limb and trunk kinematics were quantified and compared between the two groups.
Results:
Our results demonstrated that VAChT-Cre;NSE-DTA mice walked more slowly than control mice (99.2 ± 43.5 mm/s vs. 120.5 ± 27.0 mm/s) and had a longer cycle duration (0.54 ± 0.19 s vs. 0.41 ± 0.09 s). In addition, the hindlimb was comparatively more flexed during the stance phase, the trunk was more rounded and humpbacked, and the cervix was lower in VAChT-Cre;NSE-DTA mice than in the control mice during locomotion.
Discussion:
These characteristic differences in the gait kinematics might be attributed to a malfunctioning of the motor units with slow-twitch fatigue-resistant and fast-twitch fatigue-resistant types in VAChT-Cre;NSE-DTA mice. The basic description of the locomotor characteristics of this transgenic mouse line may serve as a basis for future comparative analyses.
Insights
VAChT-Cre;NSE-DTA mice exhibit altered locomotion due to motor neuron targeting. Kinematic analysis reveals slower walking speeds and distinct gait patterns in these mice, offering insights into motor neuron function.
Area of Science:
- Neuroscience
- Motor Neuron Physiology
- Animal Models
Background:
- The Vesicular Acetylcholine Transporter-Cre (VAChT-Cre) mouse line targets specific motor neurons innervating oxidative muscle fibers.
- Crossbreeding VAChT-Cre mice with NSE-DTA mice ablates these motor neurons, resulting in a model exhibiting motor deficits.
Purpose of the Study:
- To investigate the locomotor phenotype of VAChT-Cre;NSE-DTA mice using detailed kinematic analysis.
- To characterize the gait abnormalities resulting from the targeted ablation of specific motor neuron populations.
Main Methods:
- Quadrupedal walking was analyzed using X-ray fluoroscopy in VAChT-Cre;NSE-DTA and control mice.
- Quantification of stride duration, stride length, footfall patterns, and limb/trunk kinematics.
Main Results:
- VAChT-Cre;NSE-DTA mice displayed significantly slower walking speeds (99.2 mm/s) compared to controls (120.5 mm/s).
- These mice exhibited longer cycle durations, increased hindlimb flexion during stance, and altered trunk posture (more rounded, humpbacked).
Conclusions:
- Gait kinematic differences are likely due to malfunctioning slow-twitch and fast-twitch fatigue-resistant motor units.
- This study provides a foundational kinematic description of the VAChT-Cre;NSE-DTA mouse model for future research.
