Abstract
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 category for which few models exist. Here, the methods used to develop the first three‐dimensional (3D) model of a mouse hindlimb and pelvis are described. 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 micro‐computed tomography (CT) scanning and digital segmentation. The model allowed muscle moment arms as well as muscle forces 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 the 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.
Highlights
This paper describes the construction of a three-dimensional (3D) musculoskeletal model of the mouse hindlimb and pelvis
Sensitivity analysis The output of the musculoskeletal model can be represented as the isometric moment that can be produced by a muscle throughout the range of motion of any respective joint, which is a function of both its force-generating properties and its musculoskeletal geometry
A sensitivity analysis was carried out to determine the relative effect of changing muscle force-generating parameters or geometry on the model output
Summary
Mice (Mus musculus) are currently among the most common laboratory animals used in research into vertebrate locomotor behaviour, in studies into various states of neuromuscular disease or injury progression (Mancuso et al 2011; Mathur et al 2011; Ohri et al 2013; Aartsma-Rus & Van Putten, 2014; Delavar et al 2014; Brault et al 2015), or the sensory mechanics underlying locomotorAccepted for publication 2 February 2016 Article published online 12 May 2016 control (Nakanishi & Whelan, 2012; Akay et al 2014). Given that mice are close to the ancestral mammalian morphological condition (O’Leary et al 2013), discerning how locomotion is controlled in the hindlimb of these non-cursorial rodents could allow insights into how this and other hindlimb functions evolved within the mammalian lineage. Despite the value of understanding how the hindlimbs of mice function, exactly how various motor tasks are controlled within the context of the mouse hindlimb has not. While the tools for genetically targeting and subsequently manipulating specific motor or sensory pathways are in their infancy (Deisseroth, 2011), they are expanding (Llewellyn et al 2010; Iyer & Delp, 2014; Iyer et al 2014), and are most powerful in mice, making a computational model of a mouse hindlimb model a further important contribution, which is the goal of this study
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