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

Claire L Wood, Karla J Suchacki, Rob van 't Hof, Will P Cawthorn, Scott Dillon, Volker Straub, Sze Choong Wong, Syed F Ahmed, Colin Farquharson

Disease models & mechanisms 2020 Jan 10

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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 m dx: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: C mah-/- 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. © 2020. Published by The Company of Biologists Ltd.

Citation

Claire L Wood, Karla J Suchacki, Rob van 't Hof, Will P Cawthorn, Scott Dillon, Volker Straub, Sze Choong Wong, Syed F Ahmed, Colin Farquharson. 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. 2020 Jan 10;13(2)