Myotonic dystrophy mouse models: towards rational therapy development

Trends Mol Med. 2011 Sep;17(9):506-17. doi: 10.1016/j.molmed.2011.05.004. Epub 2011 Jul 2.


DNA repeat expansions can result in the production of toxic RNA. RNA toxicity has been best characterised in the context of myotonic dystrophy. Nearly 20 mouse models have contributed significant and complementary insights into specific aspects of this novel disease mechanism. These models provide a unique resource to test pharmacological, anti-sense, and gene-therapy therapeutic strategies that target specific events of the pathobiological cascade. Further proof-of-principle concept studies and preclinical experiments require critical and thorough analysis of the multiple myotonic dystrophy transgenic lines available. This review provides in-depth assessment of the molecular and phenotypic features of these models and their contribution towards the dissection of disease mechanisms, and compares them with the human condition. More importantly, it provides critical assessment of their suitability and limitations for preclinical testing of emerging therapeutic strategies.

Publication types

  • Review

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • CCAAT-Enhancer-Binding Protein-delta / genetics
  • CCAAT-Enhancer-Binding Protein-delta / metabolism
  • DNA Repeat Expansion / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal*
  • Exons / genetics
  • Genetic Therapy / methods
  • Humans
  • Mice
  • Mice, Transgenic
  • Myotonic Dystrophy / genetics
  • Myotonic Dystrophy / pathology*
  • Myotonic Dystrophy / therapy*
  • RNA / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism


  • Cebpd protein, mouse
  • DNA-Binding Proteins
  • Mbnl1 protein, mouse
  • RNA-Binding Proteins
  • CCAAT-Enhancer-Binding Protein-delta
  • RNA