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 mdx, mdx: Cmah(-/-) and mdx:Utrn(+/-) murine models with the C57BL/10 wild-type mouse.
DISEASE MODELS & MECHANISMS, 13 (2).
dmm040659-.
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.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: | 19 Jan 2023 00:13 |
| 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 |
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