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

R. Cardani, E. Mancinelli, G. Rotondo, V. Sansone, Giovanni Meola

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)177-182
Number of pages6
JournalEuropean journal of histochemistry : EJH
Volume50
Issue number3
Publication statusPublished - Jul 2006

Keywords

  • Immunofluorescence
  • Muscle biopsy
  • Myotonic dystrophies; MBNL1

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Cell Biology
  • Developmental Biology
  • Anatomy

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