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A comparison of the bone and growth phenotype of mdx, mdx:Cmah−/− and mdx:Utrn+/− murine models with the C57BL/10 wild-type mouse

Lookup NU author(s): Dr Claire Wood, Professor Volker Straub

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2020. Published by The Company of Biologists Ltd.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.


Publication metadata

Author(s): Wood CL, Suchaki KJ, van 't Hof R, Cawthorn WP, Dillon S, Straub V, Wong SC, Ahmed SF, Farquharson C

Publication type: Article

Publication status: Published

Journal: Disease Models and Mechanisms

Year: 2020

Volume: 13

Issue: 2

Print publication date: 10/01/2020

Online publication date: 21/11/2019

Acceptance date: 12/11/2019

Date deposited: 27/01/2020

ISSN (print): 1754-8403

ISSN (electronic): 1754-8411

Publisher: Company of Biologists

URL: https://doi.org/10.1242/dmm.040659

DOI: 10.1242/dmm.040659

PubMed id: 31754018


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