Search results for "muscular dystrophy"
showing 10 items of 103 documents
Abnormalities in alpha-dystroglycan expression in MDC1C and LGMD2I muscular dystrophies
2004
We recently identified mutations in the fukutin related protein (FKRP) gene in patients with congenital muscular dystrophy type 1C (MDC1C) and limb girdle muscular dystrophy type 2I (LGMD2I). The sarcolemma of these patients typically displays an immunocytochemical reduction of alpha-dystroglycan. In this report we extend these observations and report a clear correlation between the residual expression of alpha-dystroglycan and the phenotype. Three broad categories were identified. Patients at the severe end of the clinical spectrum (MDC1C) were compound heterozygote between a null allele and a missense mutation or carried two missense mutations and displayed a profound depletion of alpha-d…
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…
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…
Combined effect of AAV-U7-induced dystrophin exon skipping and soluble activin Type IIB receptor in mdx mice.
2012
Adeno-associated virus (AAV)-U7-mediated skipping of dystrophin-exon-23 restores dystrophin expression and muscle function in the mdx mouse model of Duchenne muscular dystrophy. Soluble activin receptor IIB (sActRIIB-Fc) inhibits signaling of myostatin and homologous molecules and increases muscle mass and function of wild-type and mdx mice. We hypothesized that combined treatment with AAV-U7 and sActRIIB-Fc may synergistically improve mdx muscle function. Bioactivity of sActRIIB-Fc on skeletal muscle was first demonstrated in wild-type mice. In mdx mice we show that AAV-U7-mediated dystrophin restoration improved specific muscle force and resistance to eccentric contractions when applied a…
MRI findings and evoked potentials in patients with myotonic dystrophy versus facioscapulohumeral dystrophy
1997
Evoked potentials recordings have been applied to many neurological disorders, localizing the lesions in the central nervous system (CNS) pathways. Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive degenerative disease involving the muscles of the face and shoulders. On the contrary, myotonic distrophy (MD), the most frequent and severe myotonic disease, is caracterized by myotonia (delay of relaxation after voluntary contraction), muscular atrophy and dystrophic changes in non-muscular tissues. In the present investigation, patients with clinically and electromyographically verified FSHD and MD were examined using somatosensory evoked potentials (SEP) and brainstem aud…
Hearing loss in facioscapulohumeral dystrophy.
1986
Bilateral sloping high frequency hearing loss of 20–90 dB was found in six out of ten patients with infantile or adolescent onset FSHD. In all cases the basic defect could be traced to the cochlea. The outer hair cells of the basal turn are predominantly affected. In 20 patients with various other forms of muscular dystrophy or neuromuscular disorders with an FSH distribution, no sensorineural hearing loss was found. Myopathology of FSHD patients extended from mild to severe, often showing inflammatory infiltrates and type I fibre atrophy, without unequivocal differences between the two groups with and without hearing loss. It is concluded that cochlear dysfunction is a specific and frequen…