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

42 Citations (Scopus)

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

Fingerprint

Molecular Pathology
Nuclear Proteins
Pathology
proteins
Myotonic Disorders
Muscles
muscles
Myotonic Dystrophy
RNA-binding proteins
RNA-Binding Proteins
alternative splicing
Alternative Splicing
fluorescent antibody technique
Fluorescent Antibody Technique
Proteins
mutants
therapeutics

Keywords

  • Immunofluorescence
  • Muscle biopsy
  • Myotonic dystrophies; MBNL1

ASJC Scopus subject areas

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

Cite this

Muscleblind-like protein 1 nuclear sequestration is a molecular pathology marker of DM1 and DM2. / Cardani, R.; Mancinelli, E.; Rotondo, G.; Sansone, V.; Meola, Giovanni.

In: European journal of histochemistry : EJH, Vol. 50, No. 3, 07.2006, p. 177-182.

Research output: Contribution to journalArticle

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