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.
Muscleblind-like protein 1 nuclear sequestration is a molecular pathology marker of DM1 and DM2 / R Cardani, E Mancinelli, G Rotondo, V Sansone, G Meola. - In: EUROPEAN JOURNAL OF HISTOCHEMISTRY. - ISSN 1121-760X. - 50:3(2006), pp. 177-182.
Muscleblind-like protein 1 nuclear sequestration is a molecular pathology marker of DM1 and DM2
R. Cardani;E. Mancinelli;V. Sansone;G. Meola
2006
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.File | Dimensione | Formato | |
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