Wood, Claire L, Suchacki, Karla J, van't Hof, Rob, Cawthorn, Will P, Dillon, Scott, Straub, Volker, Wong, Sze Choong, Ahmed, Syed F and Farquharson, Colin
(2020)
A comparison of the bone and growth phenotype of <i>mdx</i>, <i>mdx</i>: <i>Cmah</i><SUP>-/-</SUP> and <i>mdx</i>:<i>Utrn</i><SUP>+/-</SUP> murine models with the C57BL/10 wild-type mouse.
DISEASE MODELS & MECHANISMS, 13 (2).
dmm040659-.
Abstract
The muscular dystrophy X-linked (<i>mdx</i>) 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 <i>mdx:Cmah<sup>-/-</sup></i> mouse carries a human-like mutation in the <i>Cmah</i> gene and has a severe muscle phenotype, but its growth and bone development are unknown. In this study, we compared male <i>mdx</i>, <i>mdx:Utrn</i><sup>+/-</sup>, <i>mdx:Cmah<sup>-/-</sup></i> and wild-type (WT) mice at 3, 5 and 7 weeks of age to determine the suitability of the <i>mdx:Cmah<sup>-/-</sup></i> mouse as a model for assessing growth and skeletal development in DMD. The <i>m</i><i>dx:Cmah<sup>-/-</sup></i> 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 <i>mdx</i> and <i>mdx:</i><i>C</i><i>mah<sup>-/-</sup></i> mice versus WT mice at 7 weeks. Tissue mineral density was also higher in <i>mdx:Cmah<sup>-/-</sup></i> mice at 3 and 7 weeks. Gene profiling of <i>mdx:Cmah<sup>-/-</sup></i> bone identified increased expression of <i>Igf1</i>, <i>Igf1r</i> and <i>Vegfa</i> Both the <i>mdx</i> and <i>mdx:Cmah<sup>-/-</sup></i> mice showed an increased proportion of regulated bone marrow adipose tissue (BMAT) but a reduction in constitutive BMAT. The <i>mdx:Cmah<sup>-/-</sup></i> 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 <i>mdx:Cmah<sup>-/-</sup></i> 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.This article has an associated First Person interview with the first author of the paper.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Duchenne muscular dystrophy, Growth, Skeletal development, Marrow adiposity, Micro-CT, Growth plate |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 09 Dec 2019 10:19 |
| Last Modified: | 25 Jan 2024 15:57 |
| DOI: | 10.1242/dmm.040659 |
| Open Access URL: | https://dmm.biologists.org/content/early/2019/11/2... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3065153 |
Dimensions
Dimensions
