Gene Expression Analysis in Myotonic Dystrophy: Indications for a Common Molecular Pathogenic Pathway in DM1 and DM2

Authors: BOTTA, ANNALISA¹; VALLO, LAURA¹; RINALDI, FABRIZIO¹; BONIFAZI, EMANUELA²; AMATI, FRANCESCA¹; BIANCOLELLA, MICHELA¹; GAMBARDELLA, STEFANO¹; MANCINELLI, ENZO³; ANGELINI, CORRADO⁴; MEOLA, GIOVANNI⁵; NOVELLI, AND GIUSEPPE¹

Source: Gene Expression, Volume 13, Number 6, 2006 , pp. 339-351(13)

Publisher: Cognizant Communication Corporation

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Abstract:

An RNA gain-of-function of expanded transcripts is the most accredited molecular mechanism for myotonic dystrophy type 1 (DM1) and 2 (DM2). To disclose molecular parallels and divergences in pathogenesis of both disorders, we compared the expression profile of muscle biopsies from DM1 and DM2 patients to controls. DM muscle tissues showed a reduction in the major skeletal muscle chloride channel (CLCNl) and transcription factor Sp1 transcript levels and an abnormal processing of the CLCN1 and insulin receptor (IR) pre-mRNAs. No essential differences were observed in the muscle blind-like gene (MBNL1) and CUG binding protein 1 (CUGBP1) transcript levels as well as in the splicing pattern of the myotubularin-related 1 (MTMR1) gene. Macroarray analysis of 96 neuroscience-related genes revealed a considerable similar expression profile between the DM samples, reflective of a common muscle pathology origin. Using a twofold threshold, we found six misregulated genes important in calcium and potassium metabolism and in mitochondrial functions. Our results indicate that the DM1 and DM2 overlapping clinical phenotypes may derive from a common trans acting mechanism that traps and influences shared genes and proteins.

Keywords: Myotonic dystrophy; Pathogenesis; Expression analysis; Splicing; Ion channels

Document Type: Research article

Affiliations: 1: Department of Biopathology, Tor Vergata University of Rome, Rome, Italy 2: Tor Vergata Hospital, Medical Genetics Section, Rome, Italy 3: Department of Biomolecular Sciences and Biotechnologies, University of Milan, Milan, Italy 4: Department of Neurosciences, University of Padova, Padoa, Italy 5: Department of Neurology, University of Milan, IRCCS San Donato Hospital, Milan Italy

Publication date: 2006-06-01

More about this publication?

The Molecular and Cellular Biology area of Gene Expression covers all aspects of the gene including it structure, functions, and regulation in prokaryotes, eukaryotes, and viruses; molecular and cell biological aspects of cell growth and development, chromatin structure and function. These include topics such as DNA replication, DNA repair, gene transcription, transcriptional control, RNA processing, posttranscriptional control, oncogenes, molecular mechanisms of action of hormones, molecular mechanism of cellular differentiation, growth and development, protein synthesis, and posttranslational control.
The Molecular and Cellular Neuroscience area of Gene Expression covers all aspects of gene expression as described but is devoted exclusively to the nervous system in health and disease. Topics include studies of neurogenesis, development, aging, and neurodegeneration. Complex neural systems, motor control, special senses, and higher cortical function, when viewed from the perspective of gene expression, are appropriate for the journal. Research related to molecular mechanisms of drug tolerance, dependence, and withdrawal are solicited. Manuscripts on state-of-the-art methods and protocols for molecular profiling of neuronal structure and function are welcome.

Gene Expression Analysis in Myotonic Dystrophy: Indications for a Common Molecular Pathogenic Pathway in DM1 and DM2

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