Aetiology of Adolescent Idiopathic Scoliosis (AIS): investigation of the mechanism of spine deformity development using scoliotic mice model

Aims of the Study:

A better treatment for children with adolescent idiopathic scoliosis requires a better understanding of the mechanism involved in spinal deformity development. This would provide clinically important information on the biological and biomechanical mechanisms which drive the initiation and the progression of the deformity. It is obviously not possible to answer such questions in patients or normal growing children.  Hence in this study, a scoliotic mice model was used to investigate the development of the deformity from beginning to end.  The advantage with animal models is that we can not only understand the structural changes of the scoliosis but we can also study the changes at tissue, molecular and gene levels on different spinal elements at different stages of development.

Tight-skin (TSK) mice are commonly used as an animal model to study the disease development of a connective tissue disease known as Marfan syndrome (MFS). Patients with MFS typically have scoliosis. TSK mice are genetically modified to induce a disease state similar to that found in MFS.

Outcome of Research:

This study examined growth of the skeletons of TSK mice and wild-type control mice (normal mice without disease) during their period of rapid growth. The whole bodies of mice, 4–12 weeks of age, were scanned after sacrifice, by micro-computed tomography (microCT). Although the TSK mice were smaller than the control mice at 4 weeks, they experienced an

early growth spurt and by 8 weeks the height, but not the width, of the vertebral body was significantly greater in the TSK mice than the B6 mice. Measurement of the angles of scoliotic and kyphotic curves post-mortem in the mice was problematic, hence the team measured changes that develop in skeletal elements in these disorders. They found, unlike in the control mice where the pattern was diffuse, wedging (compression of the vertebrae) in TSK mice was directly related to spinal level and peaked steeply at the thoracolumbar junction. There was also significant asymmetry in length of the ribs in the TSK mice, but not in the control mice. The TSK mice thus appear to exhibit spinal deformities seen in MFS and could be a useful model for gaining understanding of the mechanisms of development of scoliosis and kyphosis in this disorder.

Publications:

Development of spinal deformities in the tight-skin mouse

Bing Li, Jill PG Urban and Jing Yu

Bone Research (2017) 5, 16053; doi:10.1038/boneres.2016.53

 

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