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0026566108
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Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member
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0033381553
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Myotonic dystrophies: How many are there?
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Mastaglia FL. Myotonic dystrophies: how many are there? Curr Opin Neurol 1999; 12:491-492.
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4344688683
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A non-DM1, non-DM2 multisystem myotonic disorder with frontotemporal dementia: Phenotype and suggestive mapping of the DM3 locus to chromosome 15q21-24
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Le Ber I, Martinez M, Campion D, et al. A non-DM1, non-DM2 multisystem myotonic disorder with frontotemporal dementia: phenotype and suggestive mapping of the DM3 locus to chromosome 15q21-24. Brain 2004; 127:1979-1992.
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Le Ber, I.1
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0035800434
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Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9
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Liquori CL, Ricker K, Moseley ML, et al. Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 2001; 293:864-867.
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Liquori, C.L.1
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Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues
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Taneja KL, McCurrach M, Schalling M, et al. Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues. J Cell Biol 1995; 128:995-1002.
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Margolis JM, Schoser BG, Moseley ML, et al. DM2 intronic expansions: evidence for CCUG accumulation without flanking sequence or effects on ZNF9 mRNA processing or protein expression. Hum Mol Genet 2006; 15:1808-1815. This excellent study demonstrated that the ZNF9 intron 1 flanking sequence is absent from CCUG ribonuclear inclusions in DM2. The authors also used homozygous DM2 muscle cells to show that ZNF9 protein levels are not different than in non-DM2 controls. Together these results suggest that the repeat expansion alone contributes to clinical manifestations in DM2.
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Margolis JM, Schoser BG, Moseley ML, et al. DM2 intronic expansions: evidence for CCUG accumulation without flanking sequence or effects on ZNF9 mRNA processing or protein expression. Hum Mol Genet 2006; 15:1808-1815. This excellent study demonstrated that the ZNF9 intron 1 flanking sequence is absent from CCUG ribonuclear inclusions in DM2. The authors also used homozygous DM2 muscle cells to show that ZNF9 protein levels are not different than in non-DM2 controls. Together these results suggest that the repeat expansion alone contributes to clinical manifestations in DM2.
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8
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Botta A, Caldarola S, Vallo L, et al. Effect of the [CCTG]n repeat expansion on ZNF9 expression in myotonic dystrophy type II (DM2). Biochim Biophys Acta 2006; 1762:329-334. Shows in lymphoblastoid cell lines from DM2 patients that ZNF9 mRNA and protein levels are not different from controls, indicating that the DM2 repeat expansion does not affect ZNF9 expression.
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Botta A, Caldarola S, Vallo L, et al. Effect of the [CCTG]n repeat expansion on ZNF9 expression in myotonic dystrophy type II (DM2). Biochim Biophys Acta 2006; 1762:329-334. Shows in lymphoblastoid cell lines from DM2 patients that ZNF9 mRNA and protein levels are not different from controls, indicating that the DM2 repeat expansion does not affect ZNF9 expression.
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9
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8944235350
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Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice
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Jansen G, Groenen PJ, Bachner D, et al. Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice. Nat Genet 1996; 13:316-324.
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RNA structure of trinucleotide repeats associated with human neurological diseases
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Sobczak K, de Mezer M, Michlewski G, et al. RNA structure of trinucleotide repeats associated with human neurological diseases. Nucleic Acids Res 2003; 31:5469-5482.
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11
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33745288299
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exp RNA is enhanced by reducing MBNL1 expression and reduced by overexpressing MBNL1 in Drosophila. Expression of human CUG-BP1 aggravated toxicity of the repeat RNA.
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exp RNA is enhanced by reducing MBNL1 expression and reduced by overexpressing MBNL1 in Drosophila. Expression of human CUG-BP1 aggravated toxicity of the repeat RNA.
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12
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Gomes-Pereira M, Foiry L, Nicole A, et al. CTG trinucleotide repeat big jumps: large expansions, small mice. PLoS Genet 2007; 3:e52. The authors describe a mouse model that exhibits intergenerational expansion of CTG repeat. When the repeat expansion is approximately 1000, the mice display growth retardation.
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Gomes-Pereira M, Foiry L, Nicole A, et al. CTG trinucleotide repeat "big jumps": large expansions, small mice. PLoS Genet 2007; 3:e52. The authors describe a mouse model that exhibits intergenerational expansion of CTG repeat. When the repeat expansion is approximately 1000, the mice display growth retardation.
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13
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0031038809
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Moderate intergenerational and somatic instability of a 55-CTG repeat in transgenic mice
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Gourdon G, Radvanyi F, Lia AS, et al. Moderate intergenerational and somatic instability of a 55-CTG repeat in transgenic mice. Nat Genet 1997; 15:190-192.
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Myotonic dystrophy associated expanded CUG repeat muscleblind positive ribonuclear foci are not toxic to Drosophila
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Houseley JM, Wang Z, Brock GJ, et al. Myotonic dystrophy associated expanded CUG repeat muscleblind positive ribonuclear foci are not toxic to Drosophila. Hum Mol Genet 2005; 14:873-883.
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Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat
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Mankodi A, Logigian E, Callahan L, et al. Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat. Science 2000; 289:1769-1773.
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Mahadevan MS, Yadava RS, Yu Q, et al. Reversible model of RNA toxicity and cardiac conduction defects in myotonic dystrophy. Nat Genet 2006; 38:1066-1070. This paper reports surprising results that overexpression of a part of the DMPK mRNA containing a nonexpanded (5 repeat) CTG repeat elicits a DM1-like phenotype in transgenic mice. The phenotype in this model is reversible if production of the toxic RNA is stopped.
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Mahadevan MS, Yadava RS, Yu Q, et al. Reversible model of RNA toxicity and cardiac conduction defects in myotonic dystrophy. Nat Genet 2006; 38:1066-1070. This paper reports surprising results that overexpression of a part of the DMPK mRNA containing a nonexpanded (5 repeat) CTG repeat elicits a DM1-like phenotype in transgenic mice. The phenotype in this model is reversible if production of the toxic RNA is stopped.
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17
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Transgenic expression of green fluorescence protein can cause dilated cardiomyopathy
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Huang WY, Aramburu J, Douglas PS, Izumo S. Transgenic expression of green fluorescence protein can cause dilated cardiomyopathy. Nat Med 2000; 6:482-483.
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GFP expression in muscle cells impairs actin-myosin interactions: Implications for cell therapy
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Overexpression of 3′-untranslated region of the myotonic dystrophy kinase cDNA inhibits myoblast differentiation in vitro
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Sabourin LA, Tamai K, Narang MA, Korneluk RG. Overexpression of 3′-untranslated region of the myotonic dystrophy kinase cDNA inhibits myoblast differentiation in vitro. J Biol Chem 1997; 272:29626-29635.
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The myotonic dystrophy expanded CUG repeat tract is necessary but not sufficient to disrupt C2C12 myoblast differentiation
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HnRNPH inhibits nuclear export of mRNA containing expanded CUG repeats and a distal branch point sequence
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CUG repeats present in myotonin kinase RNA form metastable "slippery" hairpins
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Expanded CUG repeat RNAs form hairpins that activate the double-stranded RNA-dependent protein kinase PKR
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RNA CUG repeats sequester CUGBP1 and alter protein levels and activity of CUGBP1
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MBNL1 is the primary determinant of focus formation and aberrant insulin receptor splicing in DM1
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exp RNA and loss of MBNL1 protein have equivalent effects on regulation of alternative splicing in mouse muscle, and that these effects are very similar to human DM1 and DM2. The authors quantify the sequestration of MBNL1 protein in DM1 and DM2 muscle, directly showing that this splicing factor is depleted from the nucleoplasm.
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exp RNA and loss of MBNL1 protein have equivalent effects on regulation of alternative splicing in mouse muscle, and that these effects are very similar to human DM1 and DM2. The authors quantify the sequestration of MBNL1 protein in DM1 and DM2 muscle, directly showing that this splicing factor is depleted from the nucleoplasm.
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Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy
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exp RNA interaction is a viable therapeutic strategy in myotonic dystrophy.
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exp RNA interaction is a viable therapeutic strategy in myotonic dystrophy.
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36
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Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel premRNA and hyperexcitability of skeletal muscle in myotonic dystrophy
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Mankodi A, Takahashi MP, Jiang H, et al. Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel premRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Mol Cell 2002; 10:35-44.
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Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing
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Charlet BN, Savkur RS, Singh G, et al. Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Mol Cell 2002; 10:45-53.
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Lueck JD, Mankodi A, Swanson MS, et al. Muscle chloride channel dysfunction in two mouse models of myotonic dystrophy. J Gen Physiol 2007; 129:79-94. The authors demonstrate ClC-1 channel dysfunction in whole muscle fibers from two mouse models of myotonic dystrophy, arguing in favor of chloride channelopathy as the mechanism of myotonia in myotonic dystrophy.
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Lueck JD, Mankodi A, Swanson MS, et al. Muscle chloride channel dysfunction in two mouse models of myotonic dystrophy. J Gen Physiol 2007; 129:79-94. The authors demonstrate ClC-1 channel dysfunction in whole muscle fibers from two mouse models of myotonic dystrophy, arguing in favor of chloride channelopathy as the mechanism of myotonia in myotonic dystrophy.
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Lueck JD, Lungu C, Mankodi A, et al. Chloride channelopathy in myotonic dystrophy resulting from loss of posttranscriptional regulation for CLCN1. Am J Physiol Cell Physiol 2007; 292:C1291-C1297. This shows that expression of ClC-1 chloride channel during normal development is regulated by a transition of alternative splicing. As muscle matures, the splicing machinery switches from producing isoforms that encode a truncated protein that is devoid of channel function, to full-length isoforms that encode functional ClC-1. In DM1 or MBNL1 knockout mice, the splicing outcome reverts to the immature isoform, whereby ClC-1 function is lost.
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Lueck JD, Lungu C, Mankodi A, et al. Chloride channelopathy in myotonic dystrophy resulting from loss of posttranscriptional regulation for CLCN1. Am J Physiol Cell Physiol 2007; 292:C1291-C1297. This shows that expression of ClC-1 chloride channel during normal development is regulated by a transition of alternative splicing. As muscle matures, the splicing machinery switches from producing isoforms that encode a truncated protein that is devoid of channel function, to full-length isoforms that encode functional ClC-1. In DM1 or MBNL1 knockout mice, the splicing outcome reverts to the immature isoform, whereby ClC-1 function is lost.
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41
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11144260152
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Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current
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Berg J, Jiang H, Thornton CA, Cannon SC. Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current. Neurology 2004; 63:2371-2375.
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Viral vector producing antisense RNA restores myotonic dystrophy myoblast functions
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Cytoplasmic and nuclear retained DMPK mRNAs are targets for RNA interference in myotonic dystrophy cells
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Langlois MA, Boniface C, Wang G, et al. Cytoplasmic and nuclear retained DMPK mRNAs are targets for RNA interference in myotonic dystrophy cells. J Biol Chem 2005; 280:16949-16954.
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