A comparison of the bone and growth phenotype of mdx, mdx:cmah-/- and mdx:utrn+/- murine models with the C57BL10 wildtype mouse

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.Mdx:cmah -/- mice were lighter than WT mice at 3, but heavier at 7 weeks (p=0.02) and showed an increased growth rate at 5 weeks (p=0.007). Cortical bone fraction as assessed by micro-computed tomography was greater in both mdx and mdx:cmah -/- mice v WT mice at 7 weeks (p<0.05).Tissue mineral density was also higher in mdx:cmah -/- mice at 3 (p<0.05) and 7 (p<0.01) 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.