Muscleblind-like protein 1 nuclear sequestration is a molecular pathology marker of DM1 and DM2

Eur J Histochem. Jul-Sep 2006;50(3):177-82.

Abstract

Myotonic dystrophies (DM) are repeat expansion diseases in which expanded CTG (DM1) and CCTG (DM2) repeats cause the disease. Mutant transcripts containing CUG/CCUG repeats are retained in muscle nuclei producing ribonuclear inclusions, which can bind specific RNA-binding proteins, leading to a reduction in their activity. The sequestration of muscleblind-like proteins (MBNLs), a family of alternative splicing factors, appears to be involved in splicing defects characteristic of DM pathologies. To determine whether MBNL1 nuclear sequestration is a feature of DM pathologies, we have examined the in vivo distribution of MBNL1 in muscle sections from genetically confirmed DM1 (n=7) and DM2 (n=9) patients, patients with other myotonic disorders (n=11) and from patients with disorders caused by repeat expansions, but not DM1/DM2 (n=3). The results of our immunofluorescence study indicate that, among patients examined, MBNL1 nuclear sequestration in protein foci is a molecular pathology marker of DM1 and DM2 patients where ribonuclear inclusions of transcripts with expanded CUG/CCUG repeats are also present. These findings indicate that MBNLs might be important targets for therapeutic interventions to correct some of the specific features of DM pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus
  • DNA Repeat Expansion
  • Genetic Markers*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Myotonic Dystrophy / classification
  • Myotonic Dystrophy / genetics*
  • Myotonic Dystrophy / metabolism*
  • Myotonic Dystrophy / pathology
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*

Substances

  • Genetic Markers
  • MBNL1 protein, human
  • RNA-Binding Proteins