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Charles, J. P., Cappellari, O., Spence, A. J., Wells, D. J. and Hutchinson, J. R. Muscle moment arms and sensitivity analysis of a mouse hindlimb musculoskeletal model. Journal of Anatomy. doi: 10.1111/joa.12461 (2016)  View

Musculoskeletal modelling has become a valuable tool with which to understand how neural, muscular, skeletal, and other tissues are integrated to produce movement. Most musculoskeletal modelling work has to date focused on humans or their close relatives, with few examples of quadrupedal animal limb models. A musculoskeletal model of the mouse hindlimb could have broad utility for questions in medicine, genetics, locomotion, and neuroscience. This is due to this species’ position as a premier model of human disease, having an array of genetic tools for manipulation of the animal in vivo, and being a small quadruped, a niche for which few models exist. Here we describe the methods used to develop the first three-dimensional (3D) model of a mouse hindlimb and pelvis. The model, which represents bones, joints and 39 musculotendon units, was created through a combination of previously gathered muscle architecture data from microdissections, contrast-enhanced microCT scanning and digital segmentation. The model allowed muscle moment arms as well as muscle force to be estimated for each musculotendon unit throughout a range of joint rotations. Moment arm analysis supported the reliability of musculotendon unit placement within the model, and comparison to a previously published rat hindlimb model further supported our model’s reliability. A sensitivity analysis performed on both the force-generating parameters and muscle’s attachment points of the model indicated that the maximal isometric muscle moment is generally most sensitive to changes in either tendon slack length or the coordinates of insertion, although the degree to which the moment is affected depends on several factors. This model represents the first step in the creation of a fully dynamic 3D computer model of the mouse hindlimb and pelvis that has application to neuromuscular disease, comparative biomechanics, and the neuromechanical basis of movement. Capturing the morphology and dynamics of the limb, it enables future dissection of the complex interactions between the nervous and musculoskeletal systems as well as the environment.

Related Publications
Charles, J. P., Cappellari, O. & Hutchinson, J. R. A Dynamic Simulation of Musculoskeletal Function in the Mouse Hindlimb During Trotting Locomotion. Frontiers in Bioengineering and Biotechnology 6, doi:10.3389/fbioe.2018.00061. (2018)  View

Mice are often used as animal models of various human neuromuscular diseases, and analysis of these models often requires detailed gait analysis. However, little is known of the dynamics of the mouse musculoskeletal system during locomotion. In this study, we used computer optimization procedures to create a simulation of trotting in a mouse, using a previously developed mouse hindlimb musculoskeletal model in conjunction with new experimental data, allowing muscle forces, activation patterns, and levels of mechanical work to be estimated. Analyzing musculotendon unit (MTU) mechanical work throughout the stride allowed a deeper understanding of their respective functions, with the rectus femoris MTU dominating the generation of positive and negative mechanical work during the swing and stance phases. This analysis also tested previous functional inferences of the mouse hindlimb made from anatomical data alone, such as the existence of a proximo-distal gradient of muscle function, thought to reflect adaptations for energy-efficient locomotion. The results do not strongly support the presence of this gradient within the mouse musculoskeletal system, particularly given relatively high negative net work output from the ankle plantarflexor MTUs, although more detailed simulations could test this further. This modeling analysis lays a foundation for future studies of the control of vertebrate movement through the development of neuromechanical simulations.