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

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numberdmm040659
JournalDMM Disease Models and Mechanisms
Volume13
Issue number2
DOIs
Publication statusPrint publication - Feb 2020
Externally publishedYes

Bibliographical note

© 2020. Published by The Company of Biologists Ltd.

Keywords

  • Adiposity
  • Animals
  • Biomechanical Phenomena
  • Bone Development
  • Bone Marrow/pathology
  • Bone and Bones/diagnostic imaging
  • Cancellous Bone/diagnostic imaging
  • Cortical Bone/diagnostic imaging
  • Disease Models, Animal
  • Gene Expression Regulation
  • Growth Plate/diagnostic imaging
  • Hand Strength
  • Inflammation/pathology
  • Insulin-Like Growth Factor I/metabolism
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Muscle, Skeletal/diagnostic imaging
  • Muscular Dystrophy, Duchenne/diagnostic imaging
  • Phenotype
  • RNA, Messenger/genetics
  • Tibia/diagnostic imaging
  • Utrophin/metabolism
  • X-Ray Microtomography
  • Duchenne muscular dystrophy, Growth, Skeletal development, Marrow adiposity, Micro-CT, Growth plate

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