Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans.
Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans.
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DOI：
10.1186/s13395-017-0143-9
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发表时间：
2017-11-16
期刊：
影响因子：
4.9
通讯作者：
Blemker SS
中科院分区：
文献类型：
--
作者：
Hu X;Charles JP;Akay T;Hutchinson JR;Blemker SS
小鼠是研究神经肌肉疾病和测试新治疗策略的最广泛使用的动物模型之一。然而，由于各种因素，使用小鼠模型进行的成功的临床前研究的结果往往无法应用于人类。这两个物种之间的肌肉功能差异可能是至关重要的，但往往被忽视了。这项研究的目的是评估和比较老鼠和人在行走时的肌肉漂移。最近发表的小鼠后肢和人类下肢的肌肉骨骼模型被用来模拟小鼠和人类步行过程中的肌肉-肌腱动力学，这是一种关键的日常活动。从这些模拟中计算出这两个物种中25个肌肉同源物的肌肉纤维长度变化(纤维漂移)，然后进行比较。为了了解步行中纤维漂移差异的潜在原因，还比较了一个步态周期中的关节漂移和肌肉瞬间手臂。在行走过程中，小鼠后肢的大部分肌肉(25块肌肉中的19块)的纤维漂移比人类的下肢肌肉小得多。对于这些肌肉，老鼠的纤维漂移仅为人类的48%±119%。这两个物种之间纤维漂移的差异主要是因为与人类相比，老鼠的关节漂移减少了，肌肉力矩臂更小了。由于众所周知，Duchenne肌营养不良症等进行性神经肌肉疾病是由活跃的肌肉延长积累的损伤加速的，这些结果表明，小鼠和人类行走过程中肌肉功能的生物力学差异可能会阻碍从小鼠模型获得的知识向人类的转化。这一知识将为如何更好地设计对小鼠的临床前研究以改进向人类临床试验的转化提供新的视角。本文的在线版本(10.1186/s13395-0170143-9)包含向授权用户提供的补充材料。
The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans. Recently published musculoskeletal models of the mouse hindlimb and human lower limb were used to simulate muscle-tendon dynamics during mouse and human walking, a key daily activity. Muscle fiber length changes (fiber excursions) of 25 muscle homologs in the two species were calculated from these simulations and then compared. To understand potential causes of differences in fiber excursions in walking, joint excursions and muscle moment arms were also compared across one gait cycle. Most muscles (19 out of 25 muscles) of the mouse hindlimb had much smaller fiber excursions as compared to human lower limb muscles during walking. For these muscles, fiber excursions in mice were only 48 ± 19% of those in humans. The differences in fiber excursion between the two species were primarily due to the reduced joint excursions and smaller muscle moment arms in mice as compared to humans. Since progressive neuromuscular diseases, such as Duchenne muscular dystrophy, are known to be accelerated by damage accumulated from active muscle lengthening, these results suggest that biomechanical differences in muscle function during walking between mice and humans may impede the translations of knowledge gained from mouse models to humans. This knowledge would add a fresh perspective on how pre-clinical studies on mice might be better designed to improve translation to human clinical trials. The online version of this article (10.1186/s13395-017-0143-9) contains supplementary material, which is available to authorized users.
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影响因子：
3.1
作者：
Buyse, Gunnar M.;Goemans, Nathalie;Escolar, Diana M.
通讯作者：
Escolar, Diana M.
DOI：
10.1097/00002060-200211001-00016
发表时间：
2002-11-01
影响因子：
3
作者：
Carter, GT;Abresch, RT;Fowler, WM
通讯作者：
Fowler, WM
影响因子：
3.3
作者：
Consolino, CM;Brooks, SV
通讯作者：
Brooks, SV
影响因子：
3.7
作者：
Charles JP;Cappellari O;Spence AJ;Hutchinson JR;Wells DJ
通讯作者：
Wells DJ
影响因子：
2.4
作者：
Charles JP;Cappellari O;Spence AJ;Wells DJ;Hutchinson JR
通讯作者：
Hutchinson JR