Wood, C. L., Suchaki, K. J., van ’t Hof, R., Cawthorn, W. P., Dillon, S., Straub, V., Wong, S.C. , Ahmed, S. F. and Farquharson, C. (2020) A comparison of the bone and growth phenotype of mdx, mdx:Cmah−/− and mdx:Utrn+/− murine models with the C57BL/10 wild-type mouse. Disease Models and Mechanisms, 13(2), dmm040659. (doi: 10.1242/dmm.040659) (PMID:31754018) (PMCID:PMC6994935)
|
Text
212746.pdf - Published Version Available under License Creative Commons Attribution. 10MB |
Abstract
The muscular dystrophy X-linked (mdx) mouse is commonly used as a mouse model of Duchenne muscular dystrophy (DMD). Its phenotype is, however, mild, and other mouse models have been explored. The mdx:Cmah−/− mouse carries a human-like mutation in the Cmah gene and has a severe muscle phenotype, but its growth and bone development are unknown. In this study, we compared male mdx, mdx:Utrn+/−, mdx:Cmah−/− and wild-type (WT) mice at 3, 5 and 7 weeks of age to determine the suitability of the mdx:Cmah−/− mouse as a model for assessing growth and skeletal development in DMD. The mdx:Cmah−/− mice were lighter than WT mice at 3 weeks, but heavier at 7 weeks, and showed an increased growth rate at 5 weeks. Cortical bone fraction as assessed by micro-computed tomography was greater in both mdx and mdx:Cmah−/− mice versus WT mice at 7 weeks. Tissue mineral density was also higher in mdx:Cmah−/− mice at 3 and 7 weeks. Gene profiling of mdx:Cmah−/− bone identified increased expression of Igf1, Igf1r and Vegfa. Both the mdx and mdx:Cmah−/− mice showed an increased proportion of regulated bone marrow adipose tissue (BMAT) but a reduction in constitutive BMAT. The mdx:Cmah−/− mice show evidence of catch-up growth and more rapid bone development. This pattern does not mimic the typical DMD growth trajectory and therefore the utility of the mdx:Cmah−/− mouse for studying growth and skeletal development in DMD is limited. Further studies of this model may, however, shed light on the phenomenon of catch-up growth.
| Item Type: | Articles |
|---|---|
| Additional Information: | Funding: C.L.W. is funded by the Medical Research Council/Muscular Dystrophy UK (MDUK) (MR/N020588/1). C.F. is grateful to the Biotechnology and Biological Sciences Research Council (BBSRC) for Institute Strategic Programme Grant Funding BB/ P0137321. W.P.C. is funded by the Medical Research Council (MR/M021394) and supported by a Chancellor’s Fellowship from the University of Edinburgh. W.P.C. and K.J.S. are also supported by the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Wong, Dr Jarod and Ahmed, Professor Syed Faisal |
| Authors: | Wood, C. L., Suchaki, K. J., van ’t Hof, R., Cawthorn, W. P., Dillon, S., Straub, V., Wong, S.C., Ahmed, S. F., and Farquharson, C. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
| Journal Name: | Disease Models and Mechanisms |
| Publisher: | Company of Biologists |
| ISSN: | 1754-8403 |
| ISSN (Online): | 1754-8411 |
| Published Online: | 21 November 2019 |
| Copyright Holders: | Copyright © 2020. Published by The Company of Biologists Ltd |
| First Published: | First published in Disease Models and Mechanisms 13(2):dmm040659 |
| Publisher Policy: | Reproduced under a Creative Commons license |
University Staff: Request a correction | Enlighten Editors: Update this record
Altmetric
Altmetric