X‐Ray Fluoroscopy‐Based Kinematic Analysis of Quadrupedal Locomotion in Slow and Fast Fatigue‐Resistant Motor Neuron‐Deleted Mice

Abstract

Introduction/AimsVAChT‐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.MethodsThe 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.ResultsOur 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.DiscussionThese 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.