Ono Ayumu, Inomata Daijiro, Ohgaki Lisa, Koyama Tenkei, Maeno Akiteru, Misawa Hidemi, Ogihara Naomichi
Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa, Japan.
Division of Pharmacology, Faculty of Pharmacy, Keio University, Tokyo, Japan.
Muscle Nerve. 2025 Feb;71(2):257-264. doi: 10.1002/mus.28324. Epub 2024 Dec 18.
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.
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.
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.
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.
引言/目的：VAChT-Cre是一种转基因小鼠品系，靶向支配氧化型I和IIa型肌纤维的慢收缩抗疲劳和快收缩抗疲劳运动神经元。为了消融这些神经元，将VAChT-Cre小鼠与NSE-DTA小鼠杂交，导致在Cre介导的切除后表达白喉毒素A。由此产生的VAChT-Cre;NSE-DTA小鼠表现出运动缺陷、异常运动、肌肉萎缩和震颤，使其成为研究运动神经元生理学和病理学的有用模型。在本研究中，我们进行了运动学分析以检查它们的异常运动表型。
使用X射线荧光透视系统分析VAChT-Cre;NSE-DTA小鼠和对照小鼠在500毫米丙烯酸隧道中的四足行走。对两组之间的步幅持续时间、步幅长度、落足模式以及肢体和躯干运动学进行量化和比较。
我们的结果表明，VAChT-Cre;NSE-DTA小鼠比对照小鼠走得更慢（99.2±43.5毫米/秒对120.5±27.0毫米/秒），并且周期持续时间更长（0.54±0.19秒对0.41±0.09秒）。此外，在运动过程中，VAChT-Cre;NSE-DTA小鼠的后肢在站立期相对更弯曲，躯干更圆且呈驼背状，并且颈部比对照小鼠更低。
步态运动学的这些特征差异可能归因于VAChT-Cre;NSE-DTA小鼠中慢收缩抗疲劳和快收缩抗疲劳类型的运动单位功能失调。对该转基因小鼠品系运动特征的基本描述可为未来的比较分析提供基础。
