Journal
DISEASE MODELS & MECHANISMS
Volume 13, Issue 2, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dmm.040659
Keywords
Duchenne muscular dystrophy; Growth; Skeletal development; Marrow adiposity; Micro-CT; Growth plate
Categories
Funding
- Medical Research Council/Muscular Dystrophy UK (MDUK) [MR/N020588/1]
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/P0137321]
- Medical Research Council [MR/M021394]
- University of Edinburgh
- Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund
- BBSRC [1803936, BBS/E/D/10002071] Funding Source: UKRI
- MRC [MR/N020588/1, MR/P020941/1, MR/M021394/1] Funding Source: UKRI
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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, Igf1 rand 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.
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