Kamal, B., Russell, D., Payne, A., Constante, D., Tanner, K. E. , Isaksson, H., Mathavan, N. and Cobb, S. R. (2015) Biomechanical properties of bone in a mouse model of Rett syndrome. Bone, 71, pp. 106-114. (doi: 10.1016/j.bone.2014.10.008) (PMID:25445449) (PMCID:PMC4289916)
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Abstract
Rett syndrome (RTT) is an X-linked genetic disorder and a major cause of intellectual disability in girls. Mutations in the methyl-CpG binding protein 2 (<i>MECP2</i>) gene are the primary cause of the disorder. Despite the dominant neurological phenotypes, <i>MECP2</i> is expressed ubiquitously throughout the body and a number of peripheral phenotypes such as scoliosis, reduced bone mineral density and skeletal fractures are also common and important clinical features of the disorder. In order to explore whether MeCP2 protein deficiency results in altered structural and functional properties of bone and to test the potential reversibility of any defects, we have conducted a series of histological, imaging and biomechanical tests of bone in a functional knockout mouse model of RTT. Both hemizygous <i>Mecp2</i><sup>stop/y</sup> male mice in which <i>Mecp2</i> is silenced in all cells and female <i>Mecp2</i><sup>stop/+</sup> mice in which <i>Mecp2</i> is silenced in ~ 50% of cells as a consequence of random X-chromosome inactivation, revealed significant reductions in cortical bone stiffness, microhardness and tensile modulus. Microstructural analysis also revealed alterations in both cortical and cancellous femoral bone between wild-type and MeCP2-deficient mice. Furthermore, unsilencing of <i>Mecp2</i> in adult mice cre-mediated stop cassette deletion resulted in a restoration of biomechanical properties (stiffness, microhardness) towards wild-type levels. These results show that MeCP2-deficiency results in overt, but potentially reversible, alterations in the biomechanical integrity of bone and highlights the importance of targeting skeletal phenotypes in considering the development of pharmacological and gene-based therapies.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Kamal, Dr Bushra and Payne, Professor Anthony and Tanner, Professor Kathleen and Cobb, Dr Stuart and Russell, Mr David |
| Authors: | Kamal, B., Russell, D., Payne, A., Constante, D., Tanner, K. E., Isaksson, H., Mathavan, N., and Cobb, S. R. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Life Sciences College of Science and Engineering > School of Engineering > Biomedical Engineering |
| Journal Name: | Bone |
| Publisher: | Elsevier |
| ISSN: | 8756-3282 |
| ISSN (Online): | 1873-2763 |
| Copyright Holders: | Copyright © 2014 The Authors |
| First Published: | First published in Bone 71:106-114 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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