Animals on Earth need to hold postures and execute a series of movements under gravity and atmospheric pressure. VAChT-Cre is a transgenic Cre driver mouse line that expresses Cre recombinase selectively in motor neurons of S-type (slow-twitch fatigue-resistant) and FR-type (fast-twitch fatigue-resistant). Sequential motor unit recruitment is a fundamental principle for fine and smooth locomotion; smaller-diameter motor neurons (S-type, FR-type) first contract low-intensity oxidative type I and type IIa muscle fibers, and thereafter larger-diameter motor neurons (FInt-type, FF-type) are recruited to contract high-intensity glycolytic type IIx and type IIb muscle fibers. To selectively eliminate S- and FR-type motor neurons, VAChT-Cre mice were crossbred with NSE-DTA mice in which the cytotoxic diphtheria toxin A fragment (DTA) was expressed in Cre-expressing neurons. The VAChT-Cre;NSE-DTA mice were born normally but progressively manifested various characteristics, including body weight loss, kyphosis, kinetic and postural tremor, and muscular atrophy. The progressive kinetic and postural tremor was remarkable from around 20 weeks of age and aggravated. Muscular atrophy was apparent in slow muscles, but not in fast muscles. The increase in motor unit number estimation was detected by electromyography, reflecting compensatory re-innervation by remaining FInt- and FF-type motor neurons to the orphaned slow muscle fibers. The muscle fibers gradually manifested fast/slow hybrid phenotypes, and the remaining FInt-and FF-type motor neurons gradually disappeared. These results suggest selective ablation of S- and FR-type motor neurons induces progressive muscle fiber-type transition, exhaustion of remaining FInt- and FF-type motor neurons, and late-onset kinetic and postural tremor in mice.

中文翻译：

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小鼠出生后慢速和快速抗疲劳运动神经元的类型选择性消融可诱导纤维类型转变和肌病后迟发的动力性和姿势性震颤

地球上的动物需要在重力和大气压力下保持姿势并执行一系列动作。 VAChT-Cre 是转基因 Cre 驱动小鼠系，在 S 型（抗慢肌疲劳）和 FR 型（抗快肌疲劳）运动神经元中选择性表达 Cre 重组酶。顺序运动单位募集是精细和平稳运动的基本原则；较小直径的运动神经元（S 型、FR 型）首先收缩低强度氧化型 I 型和 IIa 型肌纤维，然后较大直径的运动神经元（FInt 型、FF 型）被招募来收缩高强度氧化型肌纤维。 IIx 型和 IIb 型糖酵解肌纤维的强度。为了选择性消除 S 型和 FR 型运动神经元，将 VAChT-Cre 小鼠与 NSE-DTA 小鼠杂交，其中细胞毒性白喉毒素 A 片段 (DTA) 在表达 Cre 的神经元中表达。 VAChT-Cre;NSE-DTA小鼠出生时正常，但逐渐表现出各种特征，包括体重减轻、驼背、运动性和姿势性震颤以及肌肉萎缩。进行性震颤从20周龄左右开始就显着并加剧。肌肉萎缩在慢肌中很明显，但在快肌中则不明显。通过肌电图检测到运动单位数量估计的增加，反映了剩余 FInt 型和 FF 型运动神经元对孤立慢肌纤维的代偿性重新神经支配。肌纤维逐渐表现出快/慢混合表型，剩余的FInt型和FF型运动神经元逐渐消失。这些结果表明，选择性消融 S 型和 FR 型运动神经元会诱导进行性肌纤维类型转变、剩余 FInt 型和 FF 型运动神经元的耗竭，以及小鼠迟发性运动和姿势性震颤。