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Altered expression and splicing of $Ca^{2+}$metabolism genes in myotonic dystrophies DM1 and DM2
| Content Provider | Scilit |
|---|---|
| Author | Vihola, A. Sirito, M. Bachinski, L. L. Raheem, O. Screen, M. Suominen, T. Krahe, R. Udd, B. |
| Copyright Year | 2012 |
| Description | Journal: Neuropathology and applied neurobiology A. Vihola, M. Sirito, L. L. Bachinski, O. Raheem, M. Screen, T. Suominen, R. Krahe and B. Udd (2013) Neuropathology and Applied Neurobiology39, 390–405 Altered expression and splicing of $Ca^{2+}$ metabolism genes in myotonic dystrophies DM1 and DM2 Aims: Myotonic dystrophy types 1 and 2 (DM1 and DM2) are multisystem disorders caused by similar repeat expansion mutations, with similar yet distinct clinical features. Aberrant splicing of multiple effector genes, as well as dysregulation of transcription and translation, has been suggested to underlie different aspects of the complex phenotypes in DM1 and DM2. $Ca^{2+}$ plays a central role in both muscle contraction and control of gene expression, and recent expression profiling studies have indicated major perturbations of the $Ca^{2+}$ signalling pathways in DM. Here we have further investigated the expression of genes and proteins involved in $Ca^{2+}$ metabolism in DM patients, including $Ca^{2+}$ channels and $Ca^{2+}$ binding proteins. Methods: We used patient muscle biopsies to analyse mRNA expression and splicing of genes by microarray expression profiling and RT‐PCR. We studied protein expression by immunohistochemistry and immunoblotting. Results: Most of the genes studied showed mRNA up‐regulation in expression profiling. When analysed by immunohistochemistry the $Ca^{2+}$ release channel ryanodine receptor was reduced in DM1 and DM2, as was calsequestrin 2, a sarcoplasmic reticulum lumen $Ca^{2+}$ storage protein. Abnormal splicing of ATP2A1 was more pronounced in DM2 than DM1. Conclusions: We observed abnormal mRNA and protein expression in DM affecting several proteins involved in $Ca^{2+}$ metabolism, with some differences between DM1 and DM2. Our protein expression studies are suggestive of a post‐transcriptional defect(s) in the myotonic dystrophies. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882430/pdf |
| Ending Page | 405 |
| Page Count | 16 |
| Starting Page | 390 |
| e-ISSN | 13652990 |
| DOI | 10.1111/j.1365-2990.2012.01289.x |
| Journal | Neuropathology and applied neurobiology |
| Issue Number | 4 |
| Volume Number | 39 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2012-07-03 |
| Access Restriction | Open |
| Subject Keyword | Journal: Neuropathology and applied neurobiology Sport Sciences Calcium Metabolism Myotonic Dystrophy Type 1 (dm1) Myotonic Dystrophy Type 2 (dm2) Skeletal Muscle |
| Content Type | Text |
| Resource Type | Article |
