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 language | English |
|---|---|
| Pages (from-to) | 177-182 |
| Number of pages | 6 |
| Journal | European journal of histochemistry : EJH |
| Volume | 50 |
| Issue number | 3 |
| Publication status | Published - Jul 2006 |
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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 journal › Article
}
TY - JOUR
T1 - Muscleblind-like protein 1 nuclear sequestration is a molecular pathology marker of DM1 and DM2
AU - Cardani, R.
AU - Mancinelli, E.
AU - Rotondo, G.
AU - Sansone, V.
AU - Meola, Giovanni
PY - 2006/7
Y1 - 2006/7
N2 - 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.
AB - 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.
KW - Immunofluorescence
KW - Muscle biopsy
KW - Myotonic dystrophies; MBNL1
UR - http://www.scopus.com/inward/record.url?scp=34948864433&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34948864433&partnerID=8YFLogxK
M3 - Article
C2 - 16920640
AN - SCOPUS:34948864433
VL - 50
SP - 177
EP - 182
JO - European Journal of Histochemistry
JF - European Journal of Histochemistry
SN - 1121-760X
IS - 3
ER -