Search results for "Dystrophy"
showing 10 items of 268 documents
Sense and Antisense DMPK RNA Foci Accumulate in DM1 Tissues during Development.
2015
International audience; Myotonic dystrophy type 1 (DM1) is caused by an unstable expanded CTG repeat located within the DMPK gene 3'UTR. The nature, severity and age at onset of DM1 symptoms are very variable in patients. Different forms of the disease are described, among which the congenital form (CDM) is the most severe. Molecular mechanisms of DM1 are well characterized for the adult form and involve accumulation of mutant DMPK RNA forming foci in the nucleus. These RNA foci sequester proteins from the MBNL family and deregulate CELF proteins. These proteins are involved in many cellular mechanisms such as alternative splicing, transcriptional, translational and post-translational regul…
Gastric emptying, small intestinal transit and fecal output in dystrophic (mdx) mice.
2009
Duchenne muscular dystrophy (DMD), which results from deficiency in dystrophin, a sarcolemma protein of skeletal, cardiac and smooth muscle, is characterized by progressive striated muscle degeneration, but various gastrointestinal clinical manifestations have been observed. The aim was to evaluate the possible impact of the dystrophin loss on the gastrointestinal propulsion in mdx mice (animal model for DMD). The gastric emptying of a carboxymethyl cellulose/phenol red dye non-nutrient meal was not significantly different at 20 min from gavaging between wild-type and mdx mice. The intestinal transit and the fecal output were significantly decreased in mdx versus normal animals, although th…
Dystroglycan regulates structure, proliferation and differentiation of neuroepithelial cells in the developing vertebrate CNS.
2007
AbstractIn the developing CNS α- and β-dystroglycan are highly concentrated in the endfeet of radial neuroepithelial cells at the contact site to the basal lamina. We show that injection of anti-dystroglycan Fab fragments, knockdown of dystroglycan using RNAi, and overexpression of a dominant-negative dystroglycan protein by microelectroporation in neuroepithelial cells of the chick retina and optic tectum in vivo leads to the loss of their radial morphology, to hyperproliferation, to an increased number of postmitotic neurons, and to an altered distribution of several basally concentrated proteins. Moreover, these treatments also altered the oriented growth of axons from retinal ganglion c…
Bioengineered in vitro 3D model of myotonic dystrophy type 1 human skeletal muscle
2021
Abstract Myotonic dystrophy type 1 (DM1) is the most common hereditary myopathy in the adult population. The disease is characterized by progressive skeletal muscle degeneration that produces severe disability. At present, there is still no effective treatment for DM1 patients, but the breakthroughs in understanding the molecular pathogenic mechanisms in DM1 have allowed the testing of new therapeutic strategies. Animal models and in vitro two-dimensional cell cultures have been essential for these advances. However, serious concerns exist regarding how faithfully these models reproduce the biological complexity of the disease. Biofabrication tools can be applied to engineer human three-dim…
Mechanical activity of small and large intestine in normal and mdx mice: a comparative analysis.
1999
The aim of this study was to compare the motor pattern (recorded as changes in intraluminal pressure) of isolated duodenum and proximal colon between dystrophic mdx and normal mice. When duodenal recordings from control preparations were compared with mdx mice there was no significant difference in the spontaneous motor pattern, responses to electrical nerve stimulation or sensitivity to pharmacological agents. Colonic segments from mdx mice showed a more complex motor pattern, consisting of contractions with amplitude and frequency similar to those of controls and by additional contractions with lower amplitude and higher frequency. Moreover, 70% of the colonic preparations from mdx mice d…
Frozen shoulder: a sympathetic dystrophy?
2000
Diagnostic and clinical features of the frozen shoulder syndrome and the Sudeck syndrome are similar in many aspects. Radioisotope bone scan shows an increased uptake in affected areas in both diseases, while native radiographs show a progressive demineralisation. Measurement of bone mineral density (BMD) by quantitative digital radiography objectified these local decalcification processes in an early stage of the frozen shoulder syndrome; 10 of 12 patients with primary frozen shoulder had BMD decreases greater 21% in the humeral head of the affected shoulder compared to the non-affected side. In the immobilised control group with degenerative changes of the rotator cuff, calcifying tendini…
Muscleblind, BSF and TBPH are mislocalized in the muscle sarcomere of a Drosophila myotonic dystrophy model
2012
SummaryMyotonic dystrophy type 1 (DM1) is a genetic disease caused by the pathological expansion of a CTG trinucleotide repeat in the 3' UTR of the DMPK gene. In the DMPK transcripts, the CUG expansions sequester RNA-binding proteins into nuclear foci, including transcription factors and alternative splicing regulators such as MBNL1. MBNL1 sequestration has been associated with key features of DM1. However, the basis behind a number of molecular and histological alterations in DM1 remain unclear. To help identify new pathogenic components of the disease, we carried out a genetic screen using a Drosophila model of DM1 that expresses 480 interrupted CTG repeats, i(CTG)480, and a collection of…
MUSCLE BIOENERGETIC ABNORMALITY IN MYOTONIC-DYSTROPHY - A SECONDARY MITOCHONDRIAL DISORDER
1993
International audience; Abstract: The thenar muscles and gastrocnemius of a patient with myotonic dystrophy were investigated, at rest, by phosphorus nuclear magnetic resonance spectroscopy. A decrease in phosphocreatine level and an increase in inorganic phosphate and phosphodiester levels were found in the gastrocnemius, which was clinically spared, whilst the thenar muscles, which were wasted and affected by myotonia, exhibited only an increased inorganic phosphate level and an elevated pH. These findings were comparable with those found in other muscular disorders, such as Duchenne's and Becker's dystrophies, as well as in limb girdle dystrophy. They suggested that the abnormalities obs…
Aberrant glycosylation of alpha-dystroglycan causes defective binding of laminin in the muscle of chicken muscular dystrophy.
2005
Dystroglycan is a central component of dystrophin-glycoprotein complex that links extracellular matrix and cytoskeleton in skeletal muscle. Although dystrophic chicken is well established as an animal model of human muscular dystrophy, the pathomechanism leading to muscular degeneration remains unknown. We show here that glycosylation and laminin-binding activity of alpha-dystroglycan (alpha-DG) are defective in dystrophic chicken. Extensive glycan structural analysis reveals that Galbeta1-3GalNAc and GalNAc residues are increased while Siaalpha2-3Gal structure is reduced in alpha-DG of dystrophic chicken. These results implicate aberrant glycosylation of alpha-DG in the pathogenesis of mus…
Duchenne Muscular Dystrophy (DMD): Should it be Considered a Systemic Disease?
2016
Duchenne muscular dystrophy (DMD) is an X-linked muscle disease characterized by progressive skeletal muscle loss and development of respiratory failure due to involvement of respiratory muscles. Similar to human DMD, the mdx mouse model lacks dystrophin but is characterized by relatively mild muscle injury, allowing testing the effects of mild endurance exercise training on dystrophic skeletal muscle. We were interested to study the effects of exercise training on airway cells in trained mdx mice by applying the same protocol previously tested in Swiss mice. We found that mdx mice showed little airway inflammation associated with training, but developed increasing apoptosis of airway cells…