PT  - JOURNAL ARTICLE
AU  - Wood, Claire L.
AU  - Suchacki, Karla J.
AU  - van ’t Hof, Rob
AU  - Cawthorn, Will P.
AU  - Dillon, Scott
AU  - Straub, Volker
AU  - Wong, Sze Choong
AU  - Ahmed, Syed F.
AU  - Farquharson, Colin
TI  - A comparison of the bone and growth phenotype of &lt;em&gt;mdx&lt;/em&gt;, &lt;em&gt;mdx:Cmah&lt;sup&gt;−/−&lt;/sup&gt;&lt;/em&gt; and &lt;em&gt;mdx:Utrn&lt;/em&gt;&lt;em&gt;&lt;sup&gt;+/−&lt;/sup&gt;&lt;/em&gt; murine models with the C57BL/10 wild-type mouse
AID  - 10.1242/dmm.040659
DP  - 2020 Feb 01
TA  - Disease Models &amp;amp; Mechanisms
PG  - dmm040659
VI  - 13
IP  - 2
4099  - http://dmm.biologists.org/content/13/2/dmm040659.short
4100  - http://dmm.biologists.org/content/13/2/dmm040659.full
SO  - Dis Models Mech2020 Feb 01; 13
AB  - 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.