OrganismsDiseasesChemicals and DrugsPhenomena and ProcessesInformation Science
DystrophinMuscular Dystrophy, DuchenneAlgorithmsMuscular DystrophiesHominidaeMice, Inbred mdxUtrophin
Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as SPECTRIN and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa.Muscular Dystrophy, Duchenne: An X-linked recessive muscle disease caused by an inability to synthesize DYSTROPHIN, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, cardiomyopathy (see MYOCARDIAL DISEASES), and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course. (Adams et al., Principles of Neurology, 6th ed, p1415)Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Muscular Dystrophies: A heterogeneous group of inherited MYOPATHIES, characterized by wasting and weakness of the SKELETAL MUSCLE. They are categorized by the sites of MUSCLE WEAKNESS; AGE OF ONSET; and INHERITANCE PATTERNS.Hominidae: Family of the suborder HAPLORHINI (Anthropoidea) comprising bipedal primate MAMMALS. It includes modern man (HOMO SAPIENS) and the great apes: gorillas (GORILLA GORILLA), chimpanzees (PAN PANISCUS and PAN TROGLODYTES), and orangutans (PONGO PYGMAEUS).Mice, Inbred mdx: A strain of mice arising from a spontaneous MUTATION (mdx) in inbred C57BL mice. This mutation is X chromosome-linked and produces viable homozygous animals that lack the muscle protein DYSTROPHIN, have high serum levels of muscle ENZYMES, and possess histological lesions similar to human MUSCULAR DYSTROPHY. The histological features, linkage, and map position of mdx make these mice a worthy animal model of DUCHENNE MUSCULAR DYSTROPHY.Utrophin: An autosomally-encoded 376-kDa cytoskeletal protein that is similar in structure and function to DYSTROPHIN. It is a ubiquitously-expressed protein that plays a role in anchoring the CYTOSKELETON to the PLASMA MEMBRANE.

Processing of endogenous pre-mRNAs in association with SC-35 domains is gene specific. (1/1292)

Analysis of six endogenous pre-mRNAs demonstrates that localization at the periphery or within splicing factor-rich (SC-35) domains is not restricted to a few unusually abundant pre-mRNAs, but is apparently a more common paradigm of many protein-coding genes. Different genes are preferentially transcribed and their RNAs processed in different compartments relative to SC-35 domains. These differences do not simply correlate with the complexity, nuclear abundance, or position within overall nuclear space. The distribution of spliceosome assembly factor SC-35 did not simply mirror the distribution of individual pre-mRNAs, but rather suggested that individual domains contain both specific pre-mRNA(s) as well as excess splicing factors. This is consistent with a multifunctional compartment, to which some gene loci and their RNAs have access and others do not. Despite similar molar abundance in muscle fiber nuclei, nascent transcript "trees" of highly complex dystrophin RNA are cotranscriptionally spliced outside of SC-35 domains, whereas posttranscriptional "tracks" of more mature myosin heavy chain transcripts overlap domains. Further analyses supported that endogenous pre-mRNAs exhibit distinct structural organization that may reflect not only the expression and complexity of the gene, but also constraints of its chromosomal context and kinetics of its RNA metabolism.  (+info)

Hindlimb immobilization applied to 21-day-old mdx mice prevents the occurrence of muscle degeneration. (2/1292)

Dystrophin-deficient skeletal muscles of mdx mice undergo their first rounds of degeneration-regeneration at the age of 14-28 days. This feature is thought to result from an increase in motor activity at weaning. In this study, we hypothesize that if the muscle is prevented from contracting, it will avoid the degenerative changes that normally occur. For this purpose, we developed a procedure of mechanical hindlimb immobilization in 3-wk-old mice to restrain soleus (Sol) and extensor digitorum longus (EDL) muscles in the stretched or shortened position. After a 14-day period of immobilization, the striking feature was the low percentage of regenerated (centronucleated) myofibers in Sol and EDL muscles, regardless of the length at which they were fixed, compared with those on the contralateral side (stretched Sol: 8.4 +/- 6.5 vs. 46.6 +/- 10.3%, P = 0.0008; shortened Sol: 1.2 +/- 1.6 vs. 50.4 +/- 16.4%, P = 0.0008; stretched EDL: 05 +/- 0.5 vs. 32.9 +/- 17.5%, P = 0. 002; shortened EDL: 3.3 +/- 3.1 vs. 34.7 +/- 11.1%, P = 0.002). Total numbers of myofibers did not change with immobilization. This study shows that limb immobilization prevents the occurrence of the first round of myofiber necrosis in mdx mice and suggests that muscle contractions play a role in the skeletal muscle degeneration of dystrophin-deficient mdx mouse muscles.  (+info)

Increased calcium entry into dystrophin-deficient muscle fibres of MDX and ADR-MDX mice is reduced by ion channel blockers. (3/1292)

1. Single fibres were enzymatically isolated from interosseus muscles of dystrophic MDX mice, myotonic-dystrophic double mutant ADR-MDX mice and C57BL/10 controls. The fibres were kept in cell culture for up to 2 weeks for the study of Ca2+ homeostasis and sarcolemmal Ca2+ permeability. 2. Resting levels of intracellular free Ca2+, determined with the fluorescent Ca2+ indicator fura-2, were slightly higher in MDX (63 +/- 20 nM; means +/- s.d.; n = 454 analysed fibres) and ADR-MDX (65 +/- 12 nM; n = 87) fibres than in controls (51 +/- 20 nM; n = 265). 3. The amplitudes of electrically induced Ca2+ transients did not differ between MDX fibres and controls. Decay time constants of Ca2+ transients ranged between 10 and 55 ms in both genotypes. In 50 % of MDX fibres (n = 68), but in only 20 % of controls (n = 54), the decay time constants were > 35 ms. 4. Bath application of Mn2+ resulted in a progressive quench of fura-2 fluorescence emitted from the fibres. The quench rate was about 2 times higher in MDX fibres (3.98 +/- 1.9 % min-1; n = 275) than in controls (2.03 +/- 1.4 % min-1; n = 204). The quench rate in ADR-MDX fibres (2.49 +/- 1.4 % min-1; n = 87) was closer to that of controls. 5. The Mn2+ influx into MDX fibres was reduced to 10 % by Gd3+, to 19 % by La3+ and to 47 % by Ni2+ (all at 50 microM). Bath application of 50 microM amiloride inhibited the Mn2+ influx to 37 %. 6. We conclude that in isolated, resting MDX muscle fibres the membrane permeability for divalent cations is increased. The presumed additional influx of Ca2+ occurs through ion channels, but is well compensated for by effective cellular Ca2+ transport systems. The milder dystrophic phenotype of ADR-MDX mice is correlated with a smaller increase of their sarcolemmal Ca2+ permeability.  (+info)

Characterization of dystrophin and utrophin diversity in the mouse. (4/1292)

Utrophin is a 400 kDa autosomal homolog of dystrophin and a component of the submembranous cytoskeleton. While multiple dystrophin isoforms have been identified along with alternatively spliced products, to date only two different mRNA species of utrophin have been identified. To determine the degree of evolutionary conservation between dystrophin and utrophin isoforms, we have compared their expression patterns in adult mice. Northern blot analysis of multiple adult tissues confirmed that only two major sizes of transcripts are produced from each gene: 13 and 5.5 kb from utrophin and 14 and 4.8 kb from dystrophin. However, western blot analysis detected several putative short utrophin isoforms that may be homologs of the dystrophin isoforms Dp140, Dp116 and Dp71. We also identified an alternatively spliced utrophin transcript that lacks the equivalent of the alternatively spliced dystrophin exon 71. Finally, we demonstrated that the C-terminal domain of utrophin targeted to neuromuscular junctions in normal mice, but localized to the sarcolemma efficiently only in the absence of dystrophin. Our results provide further evidence for a common evolutionary origin of the utrophin and dystrophin genes.  (+info)

Ecto-ATPase activity of alpha-sarcoglycan (adhalin). (5/1292)

alpha-Sarcoglycan is a component of the sarcoglycan complex of dystrophin-associated proteins. Mutations of any of the sarcoglycan genes cause specific forms of muscular dystrophies, collectively termed sarcoglycanopathies. Importantly, a deficiency of any specific sarcoglycan affects the expression of the others. Thus, it appears that the lack of sarcoglycans deprives the muscle cell of an essential, yet unknown function. In the present study, we provide evidence for an ecto-ATPase activity of alpha-sarcoglycan. alpha-Sarcoglycan binds ATP in a Mg2+-dependent and Ca2+-independent manner. The binding is inhibited by 3'-O-(4-benzoyl)benzoyl ATP and ADP. Sequence analysis reveals the existence of a consensus site for nucleotide binding in the extracellular domain of the protein. An antibody against this sequence inhibits the binding of ATP. A dystrophin.dystrophin-associated protein preparation demonstrates a Mg-ATPase activity that is inhibited by the antibody but not by inhibitors of endo-ATPases. In addition, we demonstrate the presence in the sarcolemmal membrane of a P2X-type purinergic receptor. These data suggest that alpha-sarcoglycan may modulate the activity of P2X receptors by buffering the extracellular ATP concentration. The absence of alpha-sarcoglycan in sarcoglycanopathies leaves elevated the concentration of extracellular ATP and the persistent activation of P2X receptors, leading to intracellular Ca2+ overload and muscle fiber death.  (+info)

Characterization of the transmembrane molecular architecture of the dystroglycan complex in schwann cells. (6/1292)

We have demonstrated previously 1) that the dystroglycan complex, but not the sarcoglycan complex, is expressed in peripheral nerve, and 2) that alpha-dystroglycan is an extracellular laminin-2-binding protein anchored to beta-dystroglycan in the Schwann cell membrane. In the present study, we investigated the transmembrane molecular architecture of the dystroglycan complex in Schwann cells. The cytoplasmic domain of beta-dystroglycan was co-localized with Dp116, the Schwann cell-specific isoform of dystrophin, in the abaxonal Schwann cell cytoplasm adjacent to the outer membrane. beta-dystroglycan bound to Dp116 mainly via the 15 C-terminal amino acids of its cytoplasmic domain, but these amino acids were not solely responsible for the interaction of these two proteins. Interestingly, the beta-dystroglycan-precipitating antibody precipitated only a small fraction of alpha-dystroglycan and did not precipitate laminin and Dp116 from the peripheral nerve extracts. Our results indicate 1) that Dp116 is a component of the submembranous cytoskeletal system that anchors the dystroglycan complex in Schwann cells, and 2) that the dystroglycan complex in Schwann cells is fragile compared with that in striated muscle cells. We propose that this fragility may be attributable to the absence of the sarcoglycan complex in Schwann cells.  (+info)

Extensive but coordinated reorganization of the membrane skeleton in myofibers of dystrophic (mdx) mice. (7/1292)

We used immunofluorescence techniques and confocal imaging to study the organization of the membrane skeleton of skeletal muscle fibers of mdx mice, which lack dystrophin. beta-Spectrin is normally found at the sarcolemma in costameres, a rectilinear array of longitudinal strands and elements overlying Z and M lines. However, in the skeletal muscle of mdx mice, beta-spectrin tends to be absent from the sarcolemma over M lines and the longitudinal strands may be disrupted or missing. Other proteins of the membrane and associated cytoskeleton, including syntrophin, beta-dystroglycan, vinculin, and Na,K-ATPase are also concentrated in costameres, in control myofibers, and mdx muscle. They also distribute into the same altered sarcolemmal arrays that contain beta-spectrin. Utrophin, which is expressed in mdx muscle, also codistributes with beta-spectrin at the mutant sarcolemma. By contrast, the distribution of structural and intracellular membrane proteins, including alpha-actinin, the Ca-ATPase and dihydropyridine receptors, is not affected, even at sites close to the sarcolemma. Our results suggest that in myofibers of the mdx mouse, the membrane- associated cytoskeleton, but not the nearby myoplasm, undergoes widespread coordinated changes in organization. These changes may contribute to the fragility of the sarcolemma of dystrophic muscle.  (+info)

Membrane targeting and stabilization of sarcospan is mediated by the sarcoglycan subcomplex. (8/1292)

The dystrophin-glycoprotein complex (DGC) is a multisubunit complex that spans the muscle plasma membrane and forms a link between the F-actin cytoskeleton and the extracellular matrix. The proteins of the DGC are structurally organized into distinct subcomplexes, and genetic mutations in many individual components are manifested as muscular dystrophy. We recently identified a unique tetraspan-like dystrophin-associated protein, which we have named sarcospan (SPN) for its multiple sarcolemma spanning domains (Crosbie, R.H., J. Heighway, D.P. Venzke, J.C. Lee, and K.P. Campbell. 1997. J. Biol. Chem. 272:31221-31224). To probe molecular associations of SPN within the DGC, we investigated SPN expression in normal muscle as a baseline for comparison to SPN's expression in animal models of muscular dystrophy. We show that, in addition to its sarcolemma localization, SPN is enriched at the myotendinous junction (MTJ) and neuromuscular junction (NMJ), where it is a component of both the dystrophin- and utrophin-glycoprotein complexes. We demonstrate that SPN is preferentially associated with the sarcoglycan (SG) subcomplex, and this interaction is critical for stable localization of SPN to the sarcolemma, NMJ, and MTJ. Our experiments indicate that assembly of the SG subcomplex is a prerequisite for targeting SPN to the sarcolemma. In addition, the SG- SPN subcomplex functions to stabilize alpha-dystroglycan to the muscle plasma membrane. Taken together, our data provide important information about assembly and function of the SG-SPN subcomplex.  (+info)

A fusion peptide directs enhanced systemic dystrophin exon skipping and functional restoration in dystrophin-deficient mdx mice...A fusion peptide directs enhanced systemic dystrophin exon skipping and functional restoration in dystrophin-deficient mdx mice...
Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene that abolish the synthesis of dystrophin protein. Antisense oligonucleotides (AOs) targeted to trigger excision of an exon bearing a mutant premature stop codon in the DMD transcript have been shown to skip the mutated exon and partially restore functional dystrophin protein in dystrophin-deficient mdx mice. To fully exploit the therapeutic potential of this method requires highly efficient systemic AO delivery to multiple muscle groups, to modify the disease process and restore muscle function. While systemic delivery of naked AOs in DMD animal models requires high doses and is of relatively poor efficiency, we and others have recently shown that short arginine-rich peptide-AO conjugates can dramatically improve in vivo DMD splice correction. Here we report for the first time that a chimeric fusion peptide (B-MSP-PMO) consisting of a muscle-targeting heptapeptide (MSP) fused to an arginine-rich cell-penetrating peptide (B-peptide)
Direct visualization of the dystrophin network on skeletal muscle fiber membrane. | Journal of Cell Biology | Rockefeller...Direct visualization of the dystrophin network on skeletal muscle fiber membrane. | Journal of Cell Biology | Rockefeller...
Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene locus, is expressed on the muscle fiber surface. One key to further understanding of the cellular function of dystrophin would be extended knowledge about its subcellular organization. We have shown that dystrophin molecules are not uniformly distributed over the humen, rat, and mouse skeletal muscle fiber surface using three independent methods. Incubation of single-teased muscle fibers with antibodies to dystrophin revealed a network of denser transversal rings (costameres) and finer longitudinal interconnections. Double staining of longitudinal semithin cryosections for dystrophin and alpha-actinin showed spatial juxtaposition of the costameres to the Z bands. Where peripheral myonuclei precluded direct contact of dystrophin to the Z bands the organization of dystrophin was altered into lacunae harboring the myonucleus. These lacunae were surrounded by a dystrophin ring and covered by a more uniform dystrophin veil. ...
Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse | Read by QxMDFunctional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse | Read by QxMD
As a target for gene therapy, Duchenne muscular dystrophy (DMD) presents many obstacles but also an unparalleled prospect for correction by alternative splicing. The majority of mutations in the dystrophin gene occur in the region encoding the spectrin-like central rod domain, which is largely dispensable. Thus, splicing around mutations can generate a shortened but in-frame transcript, permitting translation of a partially functional dystrophin protein. We have tested this idea in vivo in the mdx dystrophic mouse (carrying a mutation in exon 23 of the dystrophin gene) by combining a potent transfection protocol with a 2-O-methylated phosphorothioated antisense oligoribonucleotide (2OMeAO) designed to promote skipping of the mutated exon*. The treated mice show persistent production of dystrophin at normal levels in large numbers of muscle fibers and show functional improvement of the treated muscle. Repeated administration enhances dystrophin expression without eliciting immune responses. Our ...
Exonics Therapeutics Announces Publication of Research Demonstrating Gene Repair Technology Corrected Dystrophin Expression in...Exonics Therapeutics Announces Publication of Research Demonstrating Gene Repair Technology Corrected Dystrophin Expression in...
SingleCut CRISPR efficiently restored up to 90% of dystrophin expression in skeletal and heart muscles. Study published in the journal Science Translational Medicine. CAMBRIDGE, Mass. - November 29, 2017 - Exonics Therapeutics, Inc., a biotechnology company focused on developing SingleCut CRISPR technology to repair mutations causing Duchenne muscular dystrophy and other neuromuscular diseases, today announced the publication of a preclinical study demonstrating the Companys SingleCut CRISPR technology efficiently corrected in vivo dystrophin expression in a mouse model of Duchenne.. Duchenne is a devastating muscle disease in children for which there is no cure. It is caused by mutations of the dystrophin protein gene responsible for stabilizing and protecting muscle fibers, which results in progressive muscle weakness and leads to life-threatening and ultimately fatal medical issues. Data suggest that deletions of exon 50 of the dystrophin gene are among the most common single exon deletions ...
Dystrophin deficiency exacerbates skeletal muscle pathology in dysferlin-null mice | Skeletal Muscle | Full TextDystrophin deficiency exacerbates skeletal muscle pathology in dysferlin-null mice | Skeletal Muscle | Full Text
Mutations in the genes coding for either dystrophin or dysferlin cause distinct forms of muscular dystrophy. Dystrophin links the cytoskeleton to the sarcolemma through direct interaction with β-dystroglycan. This link extends to the extracellular matrix by β-dystroglycans interaction with α-dystroglycan, which binds extracellular matrix proteins, including laminin α2, agrin and perlecan, that possess laminin globular domains. The absence of dystrophin disrupts this link, leading to compromised muscle sarcolemmal integrity. Dysferlin, on the other hand, plays an important role in the Ca2+-dependent membrane repair of damaged sarcolemma in skeletal muscle. Because dysferlin and dystrophin play different roles in maintaining muscle cell integrity, we hypothesized that disrupting sarcolemmal integrity with dystrophin deficiency would exacerbate the pathology in dysferlin-null mice and allow further characterization of the role of dysferlin in skeletal muscle. To test our hypothesis, we generated
Clinical characterisation of Becker muscular dystrophy patients predicts favourable outcome in exon-skipping therapy | Journal...Clinical characterisation of Becker muscular dystrophy patients predicts favourable outcome in exon-skipping therapy | Journal...
Objective Duchenne and Becker muscular dystrophy (DMD/BMD) are both caused by mutations in the DMD gene. Out-of-frame mutations in DMD lead to absence of the dystrophin protein, while in-frame BMD mutations cause production of internally deleted dystrophin. Clinically, patients with DMD loose ambulance around the age of 12, need ventilatory support at their late teens and die in their third or fourth decade due to pulmonary or cardiac failure. BMD has a more variable disease course. The disease course of patients with BMD with specific mutations could be very informative to predict the outcome of the exon-skipping therapy, aiming to restore the reading-frame in patients with DMD.. ...
Diagnostic strategy for the detection of dystrophin gene mutations in Asian patients and carriers using immortalized cell lines...Diagnostic strategy for the detection of dystrophin gene mutations in Asian patients and carriers using immortalized cell lines...
Tay, S.K.H.,Khng, H.H.,Low, P.S.,Lai, P.S. (2006). Diagnostic strategy for the detection of dystrophin gene mutations in Asian patients and carriers using immortalized cell lines. Journal of Child Neurology 21 (2) : 150-155. [email protected] Repository. https://doi.org/10.1177/08830738060210021101 ...
Local and distant transfection of mdx muscle fibers with dystrophin and LacZ genes delivered in vivo by synthetic microspheres ...Local and distant transfection of mdx muscle fibers with dystrophin and LacZ genes delivered in vivo by synthetic microspheres ...
Patterns of dystrophin and β-galactosidase expression were examined in mdx mice after i.m. injections of synthetic microspheres (MF-2) loaded with full-length (pHSADy) or mini-dystrophin gene (pSG5dys) cDNA plasmid constructs or with LacZ marker gene (pCMV-LacZ). A single injection of 25 μg pHSADy into quadriceps femoris muscle resulted in 6.8% of dystrophin positive myofibers (DPM) in a given muscle; 8.4% of DPM in glutaeus muscle and 4.3% of DPM in quadriceps femoris muscle of contralateral limb on day 21 after exposure compared with only 0.6% DPM in intact (non-injected) mdx mice. A high proportion of DPM (17.6% and 10.8%, respectively) was registered in both injected and contralateral muscles after mini- gene cDNA administration. MF-2/dystrophin cDNA par- ticles were detected by FISH analysis in about 60-70% of myofiber nuclei in muscles of injected and contralateral limbs 7 days after application. The presence of human dystrophin cDNA and its products in all skeletal muscles and in different
U-Ms gutted virus delivers dystrophin to muscles of adult mice with muscular dystrophyU-M's 'gutted virus' delivers dystrophin to muscles of adult mice with muscular dystrophy
Medical Center Public Relations U-M scientists have developed a viral vector that delivers the gene for dystrophin, a protein critical for normal maintenance of muscle tissue, to the muscles of adult mice with muscular dystrophy. The secret: an ordinary virus with all its natural genetic material removed to make room for the dystrophin gene which triggers production of the protein. The result: dystrophic mice with muscles producing high levels of normal dystrophin protein for several months. "We have induced long-term expression of the full-sized dystrophin protein for at least three months in the muscles of adult mice with Duchenne muscular dystrophy," says Jeffrey S. Chamberlain, associate professor of human genetics. "We have shown that mice can incorporate the gene from our viral vector into their muscle tissue. It is an encouraging result, but it is not a cure." Chamberlain presented recent results from ongoing U-M research to develop an effective gene therapy for muscular dystrophy at the ...
Dystrophin is a component of the subsynaptic membrane. | JCBDystrophin is a component of the subsynaptic membrane. | JCB
A subsynaptic protein of Mr approximately 300 kD is a major component of Torpedo electric organ postsynaptic membranes and copurifies with the AChR and the 43-kD subsynaptic protein. mAbs against this protein react with neuromuscular synapses in higher vertebrates, but not at synapses in dystrophic muscle. The Torpedo 300-kD protein comigrates in SDS-PAGE with murine dystrophin and reacts with antibodies against murine dystrophin. The sequence of a partial cDNA isolated by screening an expression library with mAbs against the Torpedo 300-kD protein shows striking homology to mammalian dystrophin, and in particular to the b isoform of dystrophin. These results indicate that dystrophin is a component of the postsynaptic membrane at neuromuscular synapses and raise the possibility that loss of dystrophin from synapses in dystrophic muscle may have consequences that contribute to muscular dystrophy. ...
Repositorio da Producao Cientifica e Intelectual da Unicamp: Bone Tissue And Muscle Dystrophin Deficiency In Mdx MiceRepositorio da Producao Cientifica e Intelectual da Unicamp: Bone Tissue And Muscle Dystrophin Deficiency In Mdx Mice
Duchenne muscular dystrophy is a neuromuscular disease caused by the lack of dystrophin that affects skeletal muscles, causing degeneration of muscle fibers and replacing them with fibrous and adipose tissue, events that gradually lead to functional loss. Patients with Duchenne muscular dystrophy have shown that bones become more fragile with age and with advancement of the disease. Muscle weakness and reduced mobility have been suggested to be the factors that promote bone deterioration. However, it seems that this does not occur in mdx mice. It has been identified in mdx mice the existence of a factor related or not to the lack of dystrophin that also participates in the impairment of bone quality. Mdx mice also exhibit muscle degeneration, but unlike human, it is compensated by muscle regeneration. In consequence, there is an increase in the muscle mass, but not necessarily of muscle contractile strength. The accommodation of this increased muscle mass promotes bone formation at specific ...
Pip5 transduction peptides direct high efficiency oligonucleotide-mediated dystrophin exon skipping in heart and phenotypic...Pip5 transduction peptides direct high efficiency oligonucleotide-mediated dystrophin exon skipping in heart and phenotypic...
Induced splice modulation of pre-mRNAs shows promise to correct aberrant disease transcripts and restore functional protein and thus has therapeutic potential. Duchenne muscular dystrophy (DMD) results from mutations that disrupt the DMD gene open reading frame causing an absence of dystrophin protein. Antisense oligonucleotide (AO)-mediated exon skipping has been shown to restore functional dystrophin in mdx mice and DMD patients treated intramuscularly in two recent phase 1 clinical trials. Critical to the therapeutic success of AO-based treatment will be the ability to deliver AOs systemically to all affected tissues including the heart. Here, we report identification of a series of transduction peptides (Pip5) as AO conjugates for enhanced systemic and particularly cardiac delivery. One of the lead peptide-AO conjugates, Pip5e-AO, showed highly efficient exon skipping and dystrophin production in mdx mice with complete correction of the aberrant DMD transcript in heart, leading to |50% of the normal
Abstract 3808: AAV-9 Micro-Dystrophin Gene Therapy Halts Heart Disease Progression in Symptomatic Dystrophic Mice | CirculationAbstract 3808: AAV-9 Micro-Dystrophin Gene Therapy Halts Heart Disease Progression in Symptomatic Dystrophic Mice | Circulation
Duchenne muscular dystrophy (DMD) is a fatal genetic disease caused by mutations in the dystrophin gene. Lack of dystrophin causes muscle wasting that eventually leads to premature death from respiratory and/or heart failure. Heart disease can be detected as early as six years of age in DMD patients. As heart disease progresses, patients begin to show overt signs of severe dilated cardiomyopathy and up to 40% of patients die from heart disease. Adeno-associated virus (AAV) mediated micro-dystrophin gene therapy brings the hope of ameliorating DMD. Dystrophin-deficient mdx mice exhibit a cardiac phenotype similar to human DMD patients albeit at a delayed progression (Bostick et al 2008 Cir Res102:121-130). Delineating the potential of gene therapy at different stages of dystrophic cardiomyopathy is critical to developing a successful gene therapy strategy. Investigators, including ourselves, have previously shown that AAV-9 can efficiently transduce the adult mouse heart. In this study, we ...
T.P.2.03 Characterisation of a complex dystrophin mutation: Assume nothing when designing exon skipping strategies - Murdoch...T.P.2.03 Characterisation of a complex dystrophin mutation: Assume nothing when designing exon skipping strategies - Murdoch...
We report an unusual and complex dystrophin gene re-arrangement that causes Duchenne muscular dystrophy, and an antisense oligonucleotide (AO) exon skipping strategy that restores the reading frame. All dystrophin exons were present, as determined by MLPA and multiplex PCR studies, while RNA analysis indicated an anomaly involving exons 49 and 50. An inversion of 28 kb was identified that lead to the omission of these exons from the mature gene transcript. In addition, multiple mRNAs arising from the variable inclusion of at least six pseudo-exons were identified. The inversion arose from an unequal recombination event, and upon characterization of the precise breakpoints in introns 48 and 50, a small duplication was identified at the proximal intron 48 breakpoint and an 11 kb deletion was found at the distal intron 50 breakpoint. Several AOs were evaluated against the two most commonly incorporated pseudo-exons (PE1 and PE2) which, when used in conjunction with an AO targeting exon 51 for ...
The subcellular distribution of chromosome 6-encoded dystrophin-related protein in the brain. | JCBThe subcellular distribution of chromosome 6-encoded dystrophin-related protein in the brain. | JCB
Chromosome 6-encoded dystrophin-related-protein (DRP) shows significant structural similarities to dystrophin at the carboxyl terminus, though the two proteins are encoded on different chromosomes. Both DRP and dystrophin are expressed in muscle and brain and show some similarity in their subcellular localization. For example, in skeletal muscle both are expressed at neuromuscular and myotendinous junctions. However, while dystrophin is absent or severely reduced in Duchenne/Becker muscular dystrophy, DRP continues to be expressed. Within the brain, dystrophin is enriched at the postsynaptic regions of specific subsets of neurons, while the distribution of DRP is yet to be described. In this study we demonstrate a distinct though highly specific pattern of distribution of DRP in the brain. DRP is enriched in the choroid plexus, pia mater, intracerebral vasculature, and ependymal lining. Within the parenchyma proper, DRP is located at the inner plasma face of astrocytic foot processes at the ...
Brain dystrophin, neurogenetics and mental retardation<...Brain dystrophin, neurogenetics and mental retardation<...
TY - JOUR. T1 - Brain dystrophin, neurogenetics and mental retardation. AU - Mehler, Mark F.. PY - 2000/3/24. Y1 - 2000/3/24. N2 - Duchenne muscular dystrophy (DMD) and the allelic disorder Becker muscular dystrophy (BMD) are common X-linked recessive neuromuscular disorders that are associated with a spectrum of genetically based developmental cognitive and behavioral disabilities. Seven promoters scattered throughout the huge DMD/BMD gene locus normally code for distinct isoforms of the gene product, dystrophin, that exhibit nervous system developmental, regional and cell-type specificity. Dystrophin is a complex plasmalemmal-cytoskeletal linker protein that possesses multiple functional domains, autosomal and X-linked homologs and associated binding proteins that form multiunit signaling complexes whose composition is unique to each cellular and developmental context. Through additional interactions with a variety of proteins of the extracellular matrix, plasma membrane, cytoskeleton and ...
Systemic delivery of human microdystrophin to regenerating mouse dystrophic muscle by muscle progenitor cells | PNASSystemic delivery of human microdystrophin to regenerating mouse dystrophic muscle by muscle progenitor cells | PNAS
Duchenne muscular dystrophy (DMD), a recessive X-linked disorder and the most common of a class of progressive muscle-wasting diseases, is characterized by the lack of dystrophin at the muscle cell membrane (1). Replacement of absent dystrophin in mdx mice by transgenic expression leads to complete restoration of normal muscle cell membrane function (2). Muscle is known to be a regenerative tissue, and this regeneration is accomplished via a heterogeneous population of cells called satellite cells or myoblasts. These cells divide upon damage to muscle, fuse to one another and with existing myofibers, and create new muscle fibers. One approach to therapy for DMD was the intramuscular injection of normal myoblasts into the skeletal muscle of DMD patients or mdx mice, which lack full-length functional dystrophin. Although early results in mdx mice were promising, the human clinical trials proved safe but ineffective, with little or no new expression of dystrophin documented (3, 4). Originally, it ...
BioNews - Molecular scalpel repairs defective muscular dystrophy DNABioNews - Molecular scalpel repairs defective muscular dystrophy DNA
UK researchers have successfully trialled a new drug to help patients with a severe form of muscular dystrophy. The new drug helps cells skip past sections of a gene damaged in Duchenne Muscular Dystrophy (DMD) so they can make smaller - but better functioning - dystrophin proteins. Dystrophin protects and connects muscle fibres. DMD affects about one in 3,500 boys who normally die in their teens or early twenties and has no cure or real treatment. Ive worked with patients with DMD for many years and this is the first time we can say with confidence that weve made a significant breakthrough towards finding a targeted treatment, said lead researcher Professor Francesco Muntoni from the Institute of Child Health, London.. Three boys, on the highest drug doses, had levels of normal dystrophin protein 18 percent (%) that of those of unaffected boys. One boys functional dystrophin level rose from near zero to 50% of normal.. The test was a phase two clinical trial, assessing which of six drug ...
Cardiac Protection after Systemic Transplant of Dystrophin Expressing Chimeric (DEC) Cells to the mdx Mouse Model of Duchenne...Cardiac Protection after Systemic Transplant of Dystrophin Expressing Chimeric (DEC) Cells to the mdx Mouse Model of Duchenne...
Duchenne Muscular Dystrophy (DMD) is a progressive lethal disease caused by X-linked mutations of the dystrophin gene. Dystrophin deficiency clinically man
multiplex PCR - oimultiplex PCR - oi
A type of polymerase chain reaction (q.v.) that is used to sample various regions of a large gene from one end to the other. For example, to analyze the human dystrophin gene, which occupies over 2 million base pairs on the X chromosome, multiplex PCR might involve simultaneous amplification from nine different sets of primers, all within the same reaction test tube. Each set of primers is chosen to produce a different-sized amplification product from a different region of the dystrophin gene. Normal males will display nine characteristic bands after the amplification products are separated by gel electrophoresis. Males with deletions in the dystrophin gene will be missing one or more of these bands. See muscular dystrophy. ...
AVV9-minidystrophin (Pfizer- PF-06939926) for Duchenne Muscular Dystrophy: Clinical Study UpdateAVV9-minidystrophin (Pfizer- PF-06939926) for Duchenne Muscular Dystrophy: Clinical Study Update
In the high-dose cohort (n=3) for whom 12-month data are available, the mean percent normal dystrophin at 12 months was 51.6% mean normal dystrophin level. Significant and Sustained Distribution of Dystrophin in muscle biopsy were observed by immunofluorescence. All clinical subject (both low does and high dose patient) showed a significant functional improvement from baseline NSAA scores after one year, compared with the scores in an independent, external control group ...
Anti-Dystrophin Antibody (Monoclonal, MANDYS8)Anti-Dystrophin Antibody (Monoclonal, MANDYS8)
Monoclonal clone# G2 antibody for DYSTROPHIN/DMD detection. Host: Mouse.Size: 100μg/vial. Tested applications: IHC-P. Reactive species: Human. DYSTROPHIN/DMD information: Molecular Weight: 425828 MW; Subcellular Localization: Cell membrane, sarcolemma ;
In vitro evaluation of novel antisense oligonucleotides is predictive of in vivo exon skipping activity for Duchenne muscular...In vitro evaluation of novel antisense oligonucleotides is predictive of in vivo exon skipping activity for Duchenne muscular...
BACKGROUND: Targeted splice modulation of pre-mRNA transcripts by antisense oligonucleotides (AOs) can correct the function of aberrant disease-related genes. Duchenne muscular dystrophy (DMD) arises as a result of mutations that interrupt the open-reading frame in the DMD gene encoding dystrophin such that dystrophin protein is absent, leading to fatal muscle degeneration. AOs have been shown to correct this dystrophin defect via exon skipping to yield functional dystrophin protein in animal models of DMD and also in DMD patients via intramuscular administration. To advance this therapeutic method requires increased exon skipping efficiency via an optimized AO sequence, backbone chemistry and additional modifications, and the improvement of methods for evaluating AO efficacy. METHODS: In the present study, we establish the conditions for rapid in vitro AO screening in H(2)K muscle cells, in which we evaluate the exon skipping properties of a number of known and novel AO chemistries [2-O-methyl,
dystrophin proteindystrophin protein
Different strategies involving stem cells for muscular dystrophy may be on the horizon, research suggests. Scientists have been using stem cells isolated from muscle tissue, bone marrow and blood vessels in lab animals to regenerate muscle fibers that are deficient in dystrophin[3] and results are encouraging.. In 2006, researchers managed to restore mobility in two afflicted dogs using stem cells isolated from muscle blood vessels [4], and in 2007 scientists managed to treat Duchenne MD in research mice using a combination of genetic correction and stem cells [3]. The latter study showed that it is possible to correct the genetic error in the cells that no longer produce dystrophin protein, and inject corrected cells stimulating the regeneration of muscles.. Researchers at the Harvard Stem Cell Institute obtained similar results, demonstrating that transplanted muscle stem cells can improve function in mice with MD, while replenishing the stem cell population in muscle fibers [5].. Although ...
Muscling out gene mutations | Science Translational MedicineMuscling out gene mutations | Science Translational Medicine
For Duchenne muscular dystrophy-the most severe and common form of a heterogeneous group of inheritable muscle wasting disorders-a solution might lie in reframing the problem. All muscular dystrophies are caused by mutations in the DMD gene, which encodes dystrophin, a large cytoplasmic protein that plays a critical role in muscle-fiber integrity. Duchenne muscular dystrophy occurs only when the DMD mutations cause reading-frame disruptions that result in nonfunctional forms of dystrophin. In contrast, in-frame deletions in the DMD gene yield internally truncated but functional dystrophins that cause a less severe form of the disease called Becker muscular dystrophy.. In a new study, Maggio and colleagues employed CRISPR/Cas9 gene editing technology to delete internal portions of the DMD gene in muscle progenitor cells from patients. By moving the DMD reading frame back on track, the authors facilitated the expression of Becker-like dystrophin proteins, which have been shown to confer ...
Exon Skipping and Dystrophin Induction in Cardiac Muscle - Muscular DystrophyExon Skipping and Dystrophin Induction in Cardiac Muscle - Muscular Dystrophy
The requirement of muscle damage for effective delivery and AON induced dystro-phin expression is further supported by the result obtained in the cardiac muscle in the mdx mice after systemic treatment of both 2OMePS AON and PMO. Cardiac muscles in mdx mice are less affected by the dystrophic process and no significant pathology and functional impairment can be obviously demonstrated until late age. Consistently, only minimum amount of dystrophin expression can be detected in the cardiac muscle even after repeated injections of both 2OMePS AON and PMO in all mdx mice aged 6 months or younger (Lu et al. 2005; Alter et al. 2006), whereas the same treatment can induce high levels of dystrophin in skeletal muscles. There is a possibility that the special tissue structure (vasculature and membrane) and pattern of metabolism or gene expression regulation could be responsible for lower efficiency of AON delivery or exon skipping inside myonuclei. However, direct injection of AON into cardiac muscles ...
Ramipril Versus Carvedilol in Duchenne and Becker Patients - Full Text View - ClinicalTrials.govRamipril Versus Carvedilol in Duchenne and Becker Patients - Full Text View - ClinicalTrials.gov
This protocol represent an open randomized and prospective trial, designed to answer the specific question regarding the role of the cardioprotective therapy in Duchenne Muscular Dystrophy and Becker Muscular Dystrophy patients. In this light, CMR could provide relevant data, reinforcing the scientific background, to start early (particularly in BMD patients in whom this is still a debated question) a cardioprotective treatment with carvedilol or ramipril.Finally,this clinical trial will clarify whether a preventive therapy may be helpful on the clinical outcome, both in reducing myocardial fibrosis and preventing the progression towards the cardiomyopathy ...
Disease Markers - Volume 25, issue 2 - Journals - IOS PressDisease Markers - Volume 25, issue 2 - Journals - IOS Press
Authors: Sura, Thanyachai , Eu-ahsunthornwattana, Jakris , Pingsuthiwong, Sarinee , Busabaratana, Manisa Article Type: Research Article Abstract: Background: Duchenne muscular dystrophy (DMD), a lethal X-linked disease affecting 1 in 3500 male births, and its more benign variant, Becker muscular dystrophy (BMD), are caused by mutations in the dystrophin gene. Because of its large size, analysing the whole gene is impractical. Methods have been developed to detect the commonest mutations i.e. the deletions of the exons. Although these tests are highly specific, their sensitivity is inherently limited by the prevalence of deletions, which differs …among different populations. Methods: We reviewed our database for the detection of Dystrophin gene mutation by means of 31-exon multiplex PCR in Thai males, diagnosed clinically and biochemically with DMD or BMD from July 1994 to November 2006. One index patient was chosen from each family for statistical analysis. The overall sensitivity of the test, ...
Monoclonal antibodies for dystrophin analysis: epitope mapping and improved binding to SDS treated muscle sections at eagle-i...Monoclonal antibodies for dystrophin analysis: epitope mapping and improved binding to SDS treated muscle sections at eagle-i...
Monoclonal antibodies for dystrophin analysis: epitope mapping and improved binding to SDS treated muscle sections is an eagle-i resource of type Journal article at eagle-i Network Shared Resource Repository.
Single cell multiplex PCR amplification of five dystrophin gene exons combined with gender determination.Single cell multiplex PCR amplification of five dystrophin gene exons combined with gender determination.
Large deletions in the dystrophin gene account for | 60% of mutations responsible for Duchenne muscular dystrophy (DMD). We have developed a genetic test that can be used directly for the preimplantation genetic diagnosis (PGD) of a majority of coupl
Sarepta eyes FDA filing for DMD drug golodirsen after positive trial - PMLiVESarepta eyes FDA filing for DMD drug golodirsen after positive trial - PMLiVE
Sarepta is preparing to file a follow-up to its Duchenne muscular dystrophy (DMD) treatment Exondys 51 that seems to have greater efficacy.. Shares in the company were on the rise after it reported positive data from a phase I/II trial of the follow-up - called golodirsen - which showed the exon-skipping drug met its primary objective of raising levels of functional dystrophin, a protein that is mutated in DMD leading to the characteristic muscle wasting symptoms.. The European trial in 25 boys with deletions in the dystrophin gene amenable to treatment with golodirsen - an exon 53-skipping drug - showed that dystrophin levels increased to 1.019% of normal from an average baseline level of 0.095% of normal, which is a 10-fold increase and superior to that seen with exon 51-targeting Exondys 51 (eteplirsen). Some clinicians have suggested however that restoring dystrophin levels to 10% may be needed to have a real clinical benefit.. Nevertheless, Sarepta is hoping that data may be enough for it ...
Study of Ataluren for Previously Treated Patients With nmDBMD in the US - Full Text View - ClinicalTrials.govStudy of Ataluren for Previously Treated Patients With nmDBMD in the US - Full Text View - ClinicalTrials.gov
Duchenne/Becker muscular dystrophy (DBMD) is a genetic disorder that develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation, is the cause of DBMD in approximately 10-15% of boys with the disease. Ataluren is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is an open-label trial for patients with nonsense mutation dystrophinopathy who received ataluren in a prior PTC-sponsored study at a US clinical trial site. This trial will be conducted at sites in the US and will evaluate the long-term safety of ataluren, as determined by adverse events and laboratory abnormalities ...
Dmdmdx/Largemyd: a new mouse model of neuromuscular diseases useful for studying physiopathological mechanisms and testing...Dmdmdx/Largemyd: a new mouse model of neuromuscular diseases useful for studying physiopathological mechanisms and testing...
Although muscular dystrophies are among the most common human genetic disorders, there are few treatment options available. Animal models have become increasingly important for testing new therapies prior to entering human clinical trials. The DMDmdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD), presenting the same molecular and protein defect as seen in humans with the disease. However, this mouse is not useful for clinical trials, because of its very mild phenotype. The mouse model for congenital myodystrophy type 1D, Largemyd, harbors a mutation in the glycosyltransferase Large gene and displays a severe phenotype. To help elucidate the role of the proteins dystrophin and LARGE in the organization of the dystrophin-glycoprotein complex in muscle sarcolemma, we generated double-mutant mice for the dystrophin and LARGE proteins. The new DMDmdx/Largemyd mouse model is viable and shows a severe phenotype that is associated with the lack of dystrophin in muscle. ...
IG1 04 Fig16IG1 04 Fig16
The human dystrophin gene extends almost 2.5 million bases, and includes a large number of exons separated by larger intron regions. Depending on the tissue type and developmental stage, any of seven different promoters (start signals) may be used to transcribe all or a part of the gene region and produce variants of the gene product. ...
Intramuscular Transplantation of Muscle Precursor Cells over-expressing MMP-9 improves Transplantation Success - PLOS Currents...Intramuscular Transplantation of Muscle Precursor Cells over-expressing MMP-9 improves Transplantation Success - PLOS Currents...
Duchenne muscular dystrophy (DMD) is a genetic disease affecting 1 out of every 3500 boys [1] . This X-linked pathology is characterized by the absence of dystrophin in muscle fibers [2] . Dystrophin is linked to several proteins in a complex named dystrophin-associated glycoprotein complex (DGC) [3] . This complex is needed for the mechanical stability of muscle fibers and its absence weakens the sarcolemma and thus makes muscle fibers less resistant to physical and mechanical stress leading to a progressive muscle degeneration [4] . DMD patients die generally between 17 and 30 years of age. There are currently no curative treatments for this disease.. When a muscle is damaged, satellite cells surrounding the damage area are activated and migrate through the basement membrane to be incorporated into the wounded muscle fiber. They need to degrade the extracellular matrix (ECM) present between fibers to reach the damaged fibers [5] . Muscle precursor cells (MPCs) transplanted in muscle either ...
Summary and Future Direction - Muscular Dystrophy - Fitness VIPSummary and Future Direction - Muscular Dystrophy - Fitness VIP
Antisense-mediated exon skipping aims to reframe dystrophin transcripts to allow generation of partly functional proteins and conversion of a severe Duchenne into a milder Becker phenotype. The first proof-of-concept in patient-derived cells was obtained in 2001 (van Deutekom et al. 2001), and the first clinical trial in DMD patients was conducted in 2006 (van Deutekom et al. 2007). This is relatively fast, especially given that AONs are a new type of drug. There are several reasons why AONs are now closer to clinical application than some of the more traditional therapeutic approached like gene and cell therapy. The exon skipping approach modulates endogenous pre-mRNA transcripts using synthetic DNA/RNA analogs. This eliminates the risks of an immune response towards viral vectors, donor-derived or autologous ex vivo modified cells and/or insertional mutagenesis. In addition, delivery of small AONs is very efficient, especially in dystrophic muscle, while efficient delivery of genes without a ...
ZFIN Publication: Bolaños-Jiménez et al., 2001ZFIN Publication: Bolaños-Jiménez et al., 2001
Dystrophin, the protein defective in Duchenne muscular dystrophy (DMD), plays a critical role in the formation and maintenance of the neuromuscular junction. In addition to dystrophin, activation of internal promoters of the DMD gene leads to the production of several short products. Among these, Dp71, which consists of the C-terminal domain of dystrophin, is the most abundant product of the gene in non-muscle tissues and brain. In this report, we compare the temporal and regional expression patterns of dystrophin and Dp71 at different stages of embryonic development and during retinal differentiation in zebrafish. The Dp71 transcripts are the earliest to be expressed at 9-10 h post-fertilization (hpf) in the axial mesoderm. As development proceeds, intense Dp71 staining is observed in the notochord, the developing brain, the marginal regions of the somites and the eye primordium. At the completion of retinal differentiation, Dp71 is expressed in the ganglion and inner nuclear layers. ...
New cures for hereditary diseases around the corner? - BioVoxNew cures for hereditary diseases around the corner? - BioVox
Duchenne muscular dystrophy (DMD) is an inherited X-linked disease that leads to severe muscular weakness. It is caused by mutations in the gene encoding dystrophin, which is responsible for connecting the cytoskeleton of muscle fibers to the extracellular matrix. The only disease-modifying therapy currently on the market is Sarepta Therapeutics Eteplirsen (Exondys 51), which targets an out-of-frame mutation implicated in 13% of DMD cases. Eteplirsen is a morpholino antisense oligomer that triggers the excision of the out-of-frame exon 51 during the pre-mRNA splicing of the dystrophin RNA transcript, leading to the production of truncated, yet functional dystrophin. Despite its approval by the FDA in 2016, Eteplirsens relatively poor efficacy has sparked a highly controversial debate. However, sales for 2017 are expected to reach approximately $125 million.. The field of DMD has seen increased gene supplementation therapy activities (e.g., Solid Biosciences is preparing an initial clinical ...
Paul Gregorevic | Quest Magazine OnlinePaul Gregorevic | Quest Magazine Online
Real progress is being made in supplying functional dystrophin genes to treat Duchenne muscular dystrophy (DMD), a disease in which mutated dystrophin genes keep this critical protein from being produced in muscle fibers. ...
Most recent papers with the keyword Ipsc derived cardiomyopathy | Read by QxMDMost recent papers with the keyword Ipsc derived cardiomyopathy | Read by QxMD
Dystrophin maintains the integrity of striated muscles by linking the actin cytoskeleton with the cell membrane. Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD) that result in progressive, debilitating muscle weakness, cardiomyopathy, and a shortened lifespan. Mutations of dystrophin that disrupt the amino-terminal actin-binding domain 1 (ABD-1), encoded by exons 2-8, represent the second-most common cause of DMD. In the present study, we compared three different strategies for CRISPR/Cas9 genome editing to correct mutations in the ABD-1 region of the DMD gene by deleting exons 3-9, 6-9, or 7-11 in human induced pluripotent stem cells (iPSCs) and by assessing the function of iPSC-derived cardiomyocytes ...
Plus itPlus it
This study is the first to demonstrate the critical role of a dystrophin isoform for the targeting and subcellular distribution of a potassium channel in glial cells. Our immunocytochemical and electrophysiological results demonstrate that functional expression of the dystrophin isoform Dp71 is necessary for the highly asymmetric expression of the inwardly rectifying potassium channel Kir4.1 in the main glial cell type in retina, the Müller cells.. Genetic inactivation of the weakly inwardly rectifying potassium channel Kir4.1 in mice demonstrated that this particular Kir subunit sets the membrane potential in Müller cells and underlies the main potassium conductance in these cells (Kofuji et al., 2000). Such marked asymmetric and clustered distribution of Kir4.1 subunits in these specialized glial cells has presumably the important physiological function of promoting the efficient buffering of extracellular potassium concentration in the retina (Newman et al., 1984). Although the cellular ...
Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy | Science Translational...Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy | Science Translational...
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BIOETYMOLOGY : ORIGIN IN BIOMEDICAL TERMS: dystrophinBIOETYMOLOGY : ORIGIN IN BIOMEDICAL TERMS: dystrophin
In the 1860s French physician Guillaume Duchenne (1806-1875) noticed that the muscles in some young boys were weakening as he believed that dystrophy progressed as muscles continued to develop without the nutrients they needed. In 1987 a protein was identified that named dystrophin because of its abnormal form causes muscular dystrophy ...
Epitopes in the interacting regions of beta dystroglycan (PPxY motif) and dystrophin (WW domain) at eagle-i Network Shared...Epitopes in the interacting regions of beta dystroglycan (PPxY motif) and dystrophin (WW domain) at eagle-i Network Shared...
Epitopes in the interacting regions of beta dystroglycan (PPxY motif) and dystrophin (WW domain) is an eagle-i resource of type Journal article at eagle-i Network Shared Resource Repository.
Dystrophin Antibody (MANDRA1(7A10)) - DSHBDystrophin Antibody (MANDRA1(7A10)) - DSHB
Monoclonal antibody against dystrophin expressed by DMD for use in Immunofluorescence, Western Blot against Fish, Human, Mouse, Xenopus
News Releases | University of Maryland School of NursingNews Releases | University of Maryland School of Nursing
DMD is a devastating, degenerative muscle disease caused by a mutation in the dystrophin gene, resulting in the absence or reduction of the dystrophin protein. Through this disease, muscle becomes fragile and easily damaged, which predisposes the patient to muscle loss and respiratory and cardiac dysfunction, leading to premature death.. "Currently there is no genetic cure for DMD. Until effective genetic therapies become available, we are focusing on identifying dysregulated pathways responsible for disease progression," Ward said. "Our ultimate goal is to design pharmacological interventions to halt or slow the progression of DMD.". Through examining DMD heart and skeletal muscle, Ward and his team have discovered that alterations in microtubules lead to an excess of calcium and reactive oxygen signals that are responsible for disease pathology. The NIH grant will enable the team to define the mechanisms that alter the microtubules in DMD muscle and determine if pharmacological ‌strategies ...
cargo cult scientist: Sereptas Cargo Plane Has Landedcargo cult scientist: Sereptas Cargo Plane Has Landed
A quick glance at Figure 1: Correlation between Two Methods Used to Quantify Dystrophin in Skeletal Muscle: Patients from Study 201/202 tells you all you need to know. As the FDA put it, "Of note, the correlation between the two independent methods used to quantify dystrophin in muscle samples was weak." They also stated, "As discussed above, we believe that immunofluorescence analysis (percent positive fibers) is not a reliable method to quantify dystrophin content." What other criticisms of Sereptas methodology did the FDA panel mention ...
Structural and biochemical characterisation of utrophin and dystrophin spectrin repeat domains : submitted in partial...Structural and biochemical characterisation of utrophin and dystrophin spectrin repeat domains : submitted in partial...
Duchenne and Becker muscular dystrophies are muscle-wasting disorders caused by mutations in the X-linked dystrophin gene. Dystrophin is a large cytoskeletal protein belonging to the spectrin superfamily, that links intracellular F-actin to the extracellular matrix via a membrane-associated glyco-protein complex thus maintaining structural rigidity and flexibility. Utrophin is a widely expressed protein that has been shown to functionally compensate for dystrophin in cultured muscle cells as well as in the muscular dystrophy mice model. Both utrophin and dystrophin share a similar domain architecture with N-terminal actin-binding domains and C-terminal variable domains separated by 22 or 24 spectrin-like repeats respectively. Therapeutic strategies to replace individuals having defective dystrophin with utrophin require full characterisation of these proteins. In this thesis, high-resolution structures of the N-terminal first spectrin repeat domains from utrophin and dystrophin have been ...
Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate...Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate...
TY - JOUR. T1 - Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: An open-label, phase 2, dose-escalation study. AU - Cirak, Sebahattin. AU - Arechavala-Gomeza, Virginia. AU - Guglieri, Michela. AU - Feng, Lucy. AU - Torelli, Silvia. AU - Anthony, Karen. AU - Abbs, Stephen. AU - Garralda, Maria Elena. AU - Bourke, John. AU - Wells, Dominic J.. AU - Dickson, George. AU - Wood, Matthew Ja. AU - Wilton, Steve D.. AU - Straub, Volker. AU - Kole, Ryszard. AU - Shrewsbury, Stephen B.. AU - Sewry, Caroline. AU - Morgan, Jennifer E.. AU - Bushby, Kate. AU - Muntoni, Francesco. PY - 2011/8/13. Y1 - 2011/8/13. N2 - We report clinical safety and biochemical efficacy from a dose-ranging study of intravenously administered AVI-4658 phosphorodiamidate morpholino oligomer (PMO) in patients with Duchenne muscular dystrophy. We undertook an open-label, phase 2, dose-escalation study (0·5, 1·0, 2·0, 4·0, ...
Differential requirement for individual sarcoglycans and dystrophin in the assembly and function of the dystrophin-glycoprotein...Differential requirement for individual sarcoglycans and dystrophin in the assembly and function of the dystrophin-glycoprotein...
Sarcoglycan is a multimeric, integral membrane glycoprotein complex that associates with dystrophin. Mutations in individual sarcoglycan subunits have been identified in inherited forms of muscular dystrophy. To evaluate the contributions of sarcoglycan and dystrophin to muscle membrane stability and muscular dystrophy, we compared muscle lacking specific sarcoglycans or dystrophin. Here we report that mice lacking (delta)-sarcoglycan developed muscular dystrophy and cardiomyopathy similar to mice lacking (gamma)-sarcoglycan. However, unlike muscle lacking (gamma)-sarcoglycan, (delta)-sarcoglycan-deficient muscle was sensitive to eccentric contraction-induced disruption of the plasma membrane. In the absence of (delta)-sarcoglycan, (alpha)-, (beta)- and (gamma)-sarcoglycan were undetectable, while dystrophin was expressed at normal levels. In contrast, without (gamma)-sarcoglycan, reduced levels of (alpha)-, (beta)- and (delta)-sarcoglycan were expressed, glycosylated and formed a complex with ...
Proteomic Characterisation of the mdx-4cv mouse model of Duchenne Muscular Dystrophy - MURAL - Maynooth University Research...Proteomic Characterisation of the mdx-4cv mouse model of Duchenne Muscular Dystrophy - MURAL - Maynooth University Research...
Duchenne muscular dystrophy is a highly complex multi-system disorder caused by primary abnormalities in the Dmd gene encoding the membrane cytoskeletal protein dystrophin. The resulting loss of the dystrophin protein triggers a concomitant disintegration of the dystrophin-associated glycoprotein complex at the sarcolemma. This complex links intracellular actin to components of the extracellular matrix and serves as a stabilising support network during normal muscle excitation-contraction-relaxation cycles. In Duchenne muscular dystrophy, the loss of dystrophin and its associated protein complex leads to membrane instability and micro-rupturing, the influx of excessive levels of calcium ions, the activation of proteases, sterile inflammation and eventually muscle degeneration and infiltration of adipose and connective tissue. Affected children suffer from severe and progressive skeletal muscle wasting with a loss of independent ambulation occurring during the early teenage years. In addition to ...
Mechanical factors tune the sensitivity of mdx muscle to eccentric strength loss and its protection by antioxidant and calcium...Mechanical factors tune the sensitivity of mdx muscle to eccentric strength loss and its protection by antioxidant and calcium...
Dystrophin deficiency sensitizes skeletal muscle of mice to eccentric contraction (ECC)-induced strength loss. ECC protocols distinguish dystrophin-deficient from healthy, wild type muscle, and test the efficacy of therapeutics for Duchenne muscular dystrophy (DMD). However, given the large lab-to-lab variability in ECC-induced strength loss of dystrophin-deficient mouse skeletal muscle (10-95%), mechanical factors of the contraction likely impact the degree of loss. Therefore, the purpose of this study was to evaluate the extent to which mechanical variables impact sensitivity of dystrophin-deficient mouse skeletal muscle to ECC. We completed ex vivo and in vivo muscle preparations of the dystrophin-deficient mdx mouse and designed ECC protocols within physiological ranges of contractile parameters (length change, velocity, contraction duration, and stimulation frequencies). To determine whether these contractile parameters affected known factors associated with ECC-induced strength loss, we measured
JCI - Stable fetal cardiomyocyte grafts in the hearts of dystrophic mice and dogs.JCI - Stable fetal cardiomyocyte grafts in the hearts of dystrophic mice and dogs.
This report documents the formation of stable fetal cardiomyocyte grafts in the myocardium of dystrophic dogs. Preliminary experiments established that the dystrophin gene product could be used to follow the fate of engrafted cardiomyocytes in dystrophic mdx mice. Importantly, ultrastructural analyses revealed the presence of intercalated discs consisting of fascia adherens, desmosomes, and gap junctions at the donor-host cardiomyocyte border. To determine if isolated cardiomyocytes could form stable intracardiac grafts in a larger species, preparations of dissociated fetal canine cardiomyocytes were delivered into the hearts of adult CXMD (canine X-linked muscular dystrophy) dogs. CXMD dogs, like Duchenne muscular dystrophy patients and mdx mice, fail to express dystrophin in both cardiac and skeletal muscle. Engrafted fetal cardiomyocytes, identified by virtue of dystrophin immunoreactivity, were observed to be tightly juxtaposed with host cardiomyocytes as long as 10 wk after engraftment, the ...
The Polyproline Site in Hinge 2 Influences the Functional Capacity of Truncated Dystrophins | proLékárníky.czThe Polyproline Site in Hinge 2 Influences the Functional Capacity of Truncated Dystrophins | proLékárníky.cz
1. HoffmanEP. BrownRHJr. KunkelLM. 1987 Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51 919 928. 2. KoenigM. HoffmanEP. BertelsonCJ. MonacoAP. FeenerC. 1987 Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 50 509 517. 3. EmeryAE. Muntoni. 2003 Duchenne Muscular Dystrophy., 3rd edn. Oxford University Press, Oxford. 4. BanksGB. FuhrerC. AdamsME. FroehnerSC. 2003 The postsynaptic submembrane machinery at the neuromuscular junction: requirement for rapsyn and the utrophin/dystrophin-associated complex. J Neurocytol 32 709 726. 5. BhasinN. LawR. LiaoG. SaferD. EllmerJ. 2005 Molecular extensibility of mini-dystrophins and a dystrophin rod construct. J Mol Biol 352 795 806. 6. ErvastiJM. 2007 Dystrophin, its interactions with other proteins, and implications for muscular dystrophy. Biochim Biophys Acta 1772 108 117. 7. ...
Genetic testing for Duchenne/Becker muscular dystrophy in Johannesburg, South AfricaGenetic testing for Duchenne/Becker muscular dystrophy in Johannesburg, South Africa
Duchenne muscular dystrophy (DMD) (OMIM #310200) is an X-linked recessive inherited muscle-wasting disease characterised primarily by progressive weakness and atrophy of the skeletal and cardiac muscle. DMD patients are typically wheelchair-bound by 12 years of age and die in their late teens or early twenties of respiratory failure. It is one of the most common Mendelian disorders, occurring in all population groups with a birth prevalence of approximately 1/3 500 males. The disease gene, DMD, linked to chromosome Xp21.2, was one of the first genes to be isolated by positional cloning,[1] and the deficient product in affected boys was then identified as the protein dystrophin.[2] Dystrophin localises to the cell membrane in muscle cells and binds the protein actin, in this way forming part of the protein complex which links the cytoskeleton with the cell membrane. The gene is extremely large, spanning 2 400 kb of genomic DNA and comprising 79 exons which encode a 14 kb transcript. Causative ...
Engineering multiple U7snRNA constructs to induce single and multiexon-skipping for Duchenne muscular dystrophy. - Nuffield...Engineering multiple U7snRNA constructs to induce single and multiexon-skipping for Duchenne muscular dystrophy. - Nuffield...
Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disorder caused by mutations in the dystrophin gene. Antisense-mediated exon skipping is one of the most promising approaches for the treatment of DMD but still faces personalized medicine challenges as different mutations found in DMD patients require skipping of different exons. However, 70% of DMD patients harbor dystrophin gene deletions in a mutation-rich area or hot-spot in the central genomic region. In this study, we have developed 11 different U7 small-nuclear RNA, to shuttle antisense sequences designed to mask key elements involved in the splicing of exons 45 to 55. We demonstrate that these constructs induce efficient exon skipping both in vitro in DMD patients myoblasts and in vivo in human DMD (hDMD) mice and that they can be combined into a single vector to achieve a multi skipping of at least 3 exons. These very encouraging results provide proof of principle that efficient multiexon-skipping can be achieved using adeno
Role of Toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle. | Kennedy Krieger InstituteRole of Toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle. | Kennedy Krieger Institute
Although the cause of Duchenne muscular dystrophy (DMD) is known, the specific factors that initiate and perpetuate disease progression are not well understood. We hypothesized that leaky dystrophin-deficient skeletal muscle releases endogenous danger signals (TLR ligands), which bind to Toll-like receptors (TLRs) on muscle and immune cells and activate downstream processes that facilitate degeneration and regeneration in dystrophic skeletal muscle. Here, we demonstrate that dystrophin-deficient mouse muscle cells show increased expression of several cell-surface and endosomal TLRs. In vitro screening identified ssRNA as a relevant endogenous TLR7 ligand. TLR7 activation led to myd88-dependent production of pro-inflammatory cytokines in dystrophin-deficient muscle cells, and cause significant degeneration/regeneration in vivo in mdx mouse muscle. Also, knockout of the central TLR adaptor protein, myd88 in mdx mice significantly improved skeletal and cardiac muscle function. Likewise, ...
MRI and MRS in Duchenne muscular dystrophy | LUMCMRI and MRS in Duchenne muscular dystrophy | LUMC
In Duchenne muscular dystrophy (DMD), a disease with a prevalence of 1 in 3500 boys, an X-linked mutation of the dystrophin gene causes absence of the dystrophin protein in the muscle cell membrane. This leads to progressive loss of muscular tissue resulting in weakness and ultimately failure of skeletal, respiratory and heart musculature. The expected lifespan of DMD boys is about 27 years. In addition, about 30% of DMD patients show cognitive impairment with an unknown etiology and prognosis. Recently, the Leiden Duchenne research group showed the first successful restoration of dystrophin expression in skeletal muscle in humans. For the further development of therapies, two advances are imperative:. ...
2 The condition | Ataluren for treating Duchenne muscular dystrophy with a nonsense mutation in the dystrophin gene | Guidance ...2 The condition | Ataluren for treating Duchenne muscular dystrophy with a nonsense mutation in the dystrophin gene | Guidance ...
Evidence-based recommendations on ataluren (Translarna) for treating Duchenne muscular dystrophy with a nonsense mutation in the dystrophin gene..
Parental origin and germline mosaicism of deletions and duplications of the dystrophin gene: a European study - Semantic ScholarParental origin and germline mosaicism of deletions and duplications of the dystrophin gene: a European study - Semantic Scholar
Knowledge about the parental origin of new mutations and the occurrence of germline mosaicism is important for estimating recurrence risks in Duchenne (DMD) and Becker muscular dystrophy (BMD). However, there are problems in resolving these issues partly because not all mutations can as yet be directly detected, and additionally because genetic ratios are very sensitive to ascertainment bias. In the present study, therefore, analysis was restricted to currently detectable mutations (deletions and duplications) in particular types of families which tend to be rare. In order to obtain sufficient data we pooled results from 25 European centers. In mothers of affected patients who were the first in their family with a dystrophin gene deletion or duplication, the ratio between the paternal and the maternal origin of this new mutation was 32:49 (binomial test P = 0.075) for DMD. In five BMD families the ratio between paternal and maternal origin of new mutations was 3∶2. Recurrence risk because of maternal
Multiple species comparison of cardiac troponin T and dystrophin: unravelling the DNA behind dilated cardiomyopathy -...Multiple species comparison of cardiac troponin T and dystrophin: unravelling the DNA behind dilated cardiomyopathy -...
Animals have frequently been used as models for human disorders and mutations. Following advances in genetic testing and treatment options, and the decreasing cost of these technologies in the clinic, mutations in both companion and commercial animals are now being investigated. A recent review highlighted the genes associated with both human and non-human dilated cardiomyopathy. Cardiac troponin T and dystrophin were observed to be associated with both human and turkey (troponin T) and canine (dystrophin) dilated cardiomyopathies. This review gives an overview of the work carried out in cardiac troponin T and dystrophin to date in both human and animal dilated cardiomyopathy.. ...
IJMS | Free Full-Text | The Role of Alpha-Dystrobrevin in Striated MuscleIJMS | Free Full-Text | The Role of Alpha-Dystrobrevin in Striated Muscle
Muscular dystrophies are a group of diseases that primarily affect striated muscle and are characterized by the progressive loss of muscle strength and integrity. Major forms of muscular dystrophies are caused by the abnormalities of the dystrophin glycoprotein complex (DGC) that plays crucial roles as a structural unit and scaffolds for signaling molecules at the sarcolemma. α-Dystrobrevin is a component of the DGC and directly associates with dystrophin. α-Dystrobrevin also binds to intermediate filaments as well as syntrophin, a modular adaptor protein thought to be involved in signaling. Although no muscular dystrophy has been associated within mutations of the α-dystrobrevin gene, emerging findings suggest potential significance of α-dystrobrevin in striated muscle. This review addresses the functional role of α-dystrobrevin in muscle as well as its possible implication for muscular dystrophy.
Structural Biochemistry/Duchenne Muscular Dystrophy - Wikibooks, open books for an open worldStructural Biochemistry/Duchenne Muscular Dystrophy - Wikibooks, open books for an open world
Dystrophin acts as a glue, which holds muscles together and maintains the structure of cells. It is also known to carry signals inside and outside of muscle fibers. Since dystrophin is carried on the X-chromosome, and boys only carry one X-chromosome, they are more susceptible to damage. Boys is considered diagnosed with Duchenne when they are unable to produce dystrophin at all. Duchenne is normally passed from parent to child but mainly occurs spontaneously.. ...
CRISPR Corrects Duchenne-Causing Mutations - CureDuchenneCRISPR Corrects Duchenne-Causing Mutations - CureDuchenne
This exciting work offers another gene-editing reagent that could potentially be used in clinical settings in the future," said Renzhi Han, who studies the molecular mechanisms of muscular dystrophies at the Ohio State University Medical Center and also was not involved in the study.. DMD, a fatal X-linked disease that results in progressively weakened skeletal and heart muscles, is caused by one of thousands of different mutations, including large deletions that disrupt the open reading of the dystrophin gene, resulting in in nonsense-mediated decay of associated messenger RNAs (mRNAs). In 2014, UT Southwesterns Eric Olson and colleagues demonstrated the ability of CRISPR-Cas9 to correct a dystrophin gene mutation in the germline of the DMD mouse model. In the present study, Olson and colleagues applied a similar strategy, but used the Cpf1 endonuclease, which differs somewhat from the widely used Streptococcus pyogenes-derived Cas9, including that it requires only a single-and shorter-guide ...
CRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes and mice | Science AdvancesCRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes and mice | Science Advances
Here, we show that the newly discovered CRISPR-Cpf1 nuclease can efficiently correct DMD mutations in patient-derived iPSCs and mdx mice, allowing for restoration of dystrophin expression. Lack of dystrophin in DMD has been shown to disrupt the integrity of the sarcolemma, causing mitochondrial dysfunction and oxidative stress (28, 29). We found increased mtDNA and higher OCRs in LbCpf1-corrected iPSC-derived cardiomyocytes compared to uncorrected DMD iPSC-derived cardiomyocytes. Metabolic abnormalities of human DMD iPSC-derived cardiomyocytes were also rescued by Cpf1-mediated genomic editing. Our findings also demonstrated the robustness and efficiency of Cpf1 in mouse genome editing. By using HDR-mediated correction, the ORF of the mouse Dmd gene was completely restored, and pathophysiological hallmarks of the dystrophic phenotype, such as fibrosis and inflammatory infiltration, were also rescued.. Two different strategies-reframing and exon skipping-were applied to restore the ORF of the DMD ...
Neuronal Dystroglycan Is Necessary for Formation and Maintenance of Functional CCK-Positive Basket Cell Terminals on Pyramidal...Neuronal Dystroglycan Is Necessary for Formation and Maintenance of Functional CCK-Positive Basket Cell Terminals on Pyramidal...
Ablation of DG in primary hippocampal culture has revealed that DG is not necessary for GABAergic synapse formation and for clustering of main GABAergic PSD proteins, including GABAARs (Lévi et al., 2002). Yet, involvement of the DGC in clustering of GABAergic postsynaptic proteins was supported by several lines of evidence. Mdx mice, used as a DMD model because of their lack of full-length dystrophin, were shown to have reduced GABAAR (but not gephyrin) clustering in the hippocampus CA1 region (Knuesel et al., 1999). Overexpression of a shorter dystrophin construct in vivo rescued the decrease of GABAAR cluster density and size, adding to the notion that dystrophin loss directly caused GABAAR clustering defects (Vaillend et al., 2010). NL2 was shown to biochemically interact with dystrophin over the intracellular synaptic scaffolding molecule S-SCAM (Sumita et al., 2007). Furthermore, a functional connection between the DGC and NL2 is suggested by the observation that, in GABAAR α2 subunit KO ...
Inheritance | Muscular Dystrophy | NCBDDD | CDCInheritance | Muscular Dystrophy | NCBDDD | CDC
The change in the gene that causes Duchenne/Becker muscular dystrophy (DBMD) happens on the X chromosome. A boy gets an X chromosome from his mother and a Y chromosome from his father. Only the X chromosome can have the changed gene that causes DBMD. Females almost never have DBMD because they have two X chromosomes. Even if a female has one X chromosome with the DBMD gene, her second X chromosome usually will make enough dystrophin to keep her muscles strong.. Because a female can carry (or have) one DBMD mutation and not be affected, she is referred to as a carrier. As a carrier, a female does have a risk of passing the same mutation on to her children. Each son born to a carrier female has a 50% chance of inheriting the DBMD mutation and having MD. Each daughter born to a carrier female instead has a 50% chance of inheriting the DBMD mutation and becoming a carrier like her mother.. Although most males diagnosed with DBMD are known to have inherited the mutation from their mothers, about ...
ResearchResearch
Skeletal muscle has tissue-specific stem cells named "satellite cells". Satellite cells exist in a quiescent state between myofibers and the basal lamina. When skeletal muscle is injured, satellite cells are activated, proliferate, and differentiate into myofibers. It is reported that isolated satellite cells/myoblasts from healthy donors are able to fuse with host dystrophin-deficient myofibers after transplantation via intramuscular injection, and expression of dystrophin at the sarcolemma was observed. Therefore, myoblast transfer is expected to be a promising therapy for DMD. However, the numbers of cells prepared from donors are not adequate for clinical use. To obtain a large number of satellite cells/ myoblasts of good quality, we are developing a method to induce muscle stem cells from human iPS cells. Although autologous cell transplantation needs no immunosuppression, the genes require editing to express dystrophin. In addition, the time and expense required for the process impose a ...
Abstract 3448: Cardiac Dystrophinopathies: Prevalence and Clinical Phenotypes in a Consecutive Series of 408 Males with...Abstract 3448: Cardiac Dystrophinopathies: Prevalence and Clinical Phenotypes in a Consecutive Series of 408 Males with...
Dystrophin gene (DYS) defects cause three major clinical phenotypes: Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and X-linked dilated cardiomyopathy (DCM). In the cardiology setting patients come to the clinical attention for DCM with/without increased serum creatine phosphokinase (sCPK) and/or myopathy. Purpose To determine the prevalence of DYS defects in a consecutive series of 408 DCM patients and to describe their phenotypes.. Methods DCM was diagnosed according to WHO criteria. The criterion for first level DYS screening was male sex: we included males with both normal and increased sCPK. The criterion for second level DYS screening was the presence of defects of myocyte immunostaining by 5′, rod, midrod and C-terminal domain using anti-DYS antibodies at endomyocardial biopsy. This latter analysis consisted of the direct automated sequencing of the 75 exons and flanking regions of the gene.. Results We identified DYS defects in 31 of the 408 probands (7.6%); the ...
Automated DNA Mutation Detection Using Universal Conditions Direct Sequencing: Application to Ten Muscular Dystrophy GenesAutomated DNA Mutation Detection Using Universal Conditions Direct Sequencing: Application to Ten Muscular Dystrophy Genes
Background: One of the most common and efficient methods for detecting mutations in genes is PCR amplification followed by direct sequencing. Until recently, the process of designing PCR assays has been to focus on individual assay parameters rather than concentrating on matching conditions for a set of assays. Primers for each individual assay were selected based on location and sequence concerns. The two primer sequences were then iteratively adjusted to make the individual assays work properly. This generally resulted in groups of assays with different annealing temperatures that required the use of multiple thermal cyclers or multiple passes in a single thermal cycler making diagnostic testing time-consuming, laborious and expensive. These factors have severely hampered diagnostic testing services, leaving many families without an answer for the exact cause of a familial genetic disease. A search of GeneTests for sequencing analysis of the entire coding sequence for genes that are known to ...
Title page for ETD etd-05262005-130324Title page for ETD etd-05262005-130324
Duchenne muscular dystrophy (DMD) is a severe and fatal muscle wasting disease characterized by a high mutation rate in the gene that encodes the membrane-associated protein dystrophin that results in absence of expressed protein. Although the primary genetic defect for DMD is known, the mechanisms that initiate the onset of DMD are not currently understood. This study tested the hypothesis that pathophysiological processes involved in DMD could be identified by the global expression of mRNA in maturing dystrophin- and utrophin-deficient mouse (mdx:utrn-/-) muscles. Two potential dystrophic onset mechanisms targeted for analysis were (1) disrupted expression of calcium handling proteins; and, (2) increased expression of immune response markers. An mRNA expression profile was developed following isolation of total RNA from control and mdx:utrn-/- triceps surae (TS) muscles at ages 9-10 and 20-21 days using Affymetrix® Mu74Av2 GeneChips®. Compared to control, the mRNA expression profile in ...
Browse School of Medicine | Stanford ProfilesBrowse School of Medicine | Stanford Profiles
Current Research and Scholarly InterestsDuchenne muscular dystrophy (DMD) is an X-chromosome-linked genetic disease that is caused by a mutation in the dystrophin gene and affects 1 in every 3500 boys. DMD patients suffer progressive muscle wasting and eventual cardiorespiratory failure that results in an early death in the second or third decade of life. Although extensive research effort has been invested, lack of a good mouse model that mimics the cardiac failure hinders research. We have developed a novel mouse model that exhibit all the symptoms found in DMD patients and our research is aimed at understanding the cardiac failure in DMD for future therapeutic interventions. Our mouse model fully recapitulates the DMD symptoms because we also took into account of the size of human protection DNA on chromosomal ends (telomere) compared to mouse. We would like to study the cause of cardiac failure in our mouse model by 1) determine if telomere shortening is specific to cardiomyocytes, 2) ...
minidystrophin gene | Quest Magazine Onlineminidystrophin gene | Quest Magazine Online
A promising "minidystrophin gene" that restores normal muscle force to skeletal and diaphragm muscles in mice with a disease resembling Duchenne muscular dystrophy (DMD) seems to be only partially effective at restoring strength and function to heart muscles. ...
Updated clinical data on Pfizers phase 1b gene therapy study - World DuchenneUpdated clinical data on Pfizer's phase 1b gene therapy study - World Duchenne
The primary endpoint of the Phase 1b study is to assess the safety and tolerability of this investigational gene therapy in ambulatory boys with Duchenne muscular dystrophy through 12 months following treatment. Based on the data to date, the most common adverse events (AEs) suspected to be related to PF-06939926 (occurring in ,40% of patients) were vomiting, nausea, decreased appetite, and pyrexia. There was no evidence of clinically relevant anti-dystrophin responses or hepatic dysfunction with the protocol-defined daily glucocorticoid regimen.. Among the 9 patients, 3 serious adverse events (SAEs) were reported in the first 14 days following administration, one more SAE than at Pfizers previous update. Importantly, each of these SAEs was fully resolved and at their last clinic visits, all patients were doing well. The first SAE involved persistent vomiting resulting in dehydration, which required admission for IV anti-emetics and fluids. The second SAE involved acute kidney injury with ...
Oalib searchOalib search
Abstract: Cultured muscle cells from DMD patients carrying duplications were transfected with AONs targeting the duplicated exons, and the dystrophin RNA and protein were analyzed.For two brothers with an exon 44 duplication, skipping was, even at suboptimal transfection conditions, so efficient that both exons 44 were skipped, thus generating, once more, an out-of-frame transcript. In such cases, one may resort to multi-exon skipping to restore the reading frame, as is shown here by inducing skipping of exon 43 and both exons 44. By contrast, in cells from a patient with an exon 45 duplication we were able to induce single exon 45 skipping, which allowed restoration of wild type dystrophin. The correction of a larger duplication (involving exons 52 to 62), by combinations of AONs targeting the outer exons, appeared problematic due to inefficient skipping and mistargeting of original instead of duplicated exons.The correction of DMD duplications by exon skipping depends on the specific exons ...
CRISPR halted muscular dystrophy in dogs. Are humans next?CRISPR halted muscular dystrophy in dogs. Are humans next?
In a study published Thursday in Science, a team led by Eric Olson at the University of Texas Southwestern Medical Center used Crispr to successfully modify the DNA of four young dogs, reversing the molecular defect responsible for their muscle wasting disease. DMD isnt an obvious candidate for Crisprs find-and-replace function; the dystrophin gene is the largest in the human genome, and there are thousands of different mutations that can all result in the disease. But Olson found a way to target an error-prone hot spot on exon 51, which he figured could, with a single slice, benefit approximately 13 percent of DMD patients.. Building on previous work he had done to correct mutations in mice and human heart cells, Olson teamed up with vets at RVC to test the approach on their beagle colony. The researchers first packed the instructions for the Crispr gene-editing components into a virus with an affinity for muscle cells. Then they injected millions of copies of that virus into four ...
MCB I Block 3MCB I Block 3
Duchennes Muscular Dystrophy: X-linked or gonadal mosaic → TOTAL loss of function of dystrophin → Gowers Maneuver, calf pseudohypertrophy (calf looks big and muscular but its not, because damage accumulates a lot of fat and connective tissue) → walk on toes, mild cognitive impairment, death by cardiac/resp failure. 8% of female carriers of DMD gene have partial weakness. Called MANIFESTING HETEROZYGOTES ...
Mast2 - Microtubule-associated serine/threonine-protein kinase 2 - Mus musculus (Mouse) - Mast2 gene & proteinMast2 - Microtubule-associated serine/threonine-protein kinase 2 - Mus musculus (Mouse) - Mast2 gene & protein
Appears to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Phosphorylation of DMD or UTRN may modulate their affinities for associated proteins. Functions in a multi-protein complex in spermatid maturation. Regulates lipopolysaccharide-induced IL-12 synthesis in macrophages by forming a complex with TRAF6, resulting in the inhibition of TRAF6 NF-kappa-B activation.
College of Biological SciencesCollege of Biological Sciences
Our objective is to fully define the function of dystrophin in striated muscle to understand how its absence or abnormality leads to the pathologies observed in Duchenne and Becker muscular dystrophies. Our unique approach integrates biochemical and biophysical analyses of the very large dystrop ...
Cellular Antennae Play A key Role In Muscle-To-Fat TransformationCellular Antennae Play A key Role In Muscle-To-Fat Transformation
Duchenne muscular dystrophy is a genetic disorder characterized by progressive muscle degeneration and weakness, and is caused by an absence of dystrophin, a protein that helps keep muscle cells intact.
Dys - Dystrophin, isoform D - Drosophila melanogaster (Fruit fly) - Dys gene & proteinDys - Dystrophin, isoform D - Drosophila melanogaster (Fruit fly) - Dys gene & protein
Required for the maintenance of appropriate synaptic retrograde communication and the stabilization of muscle cell architecture or physiology. May play a role in anchoring the cytoskeleton to the plasma membrane.
DesminDesmin
WW domainWW domain
SGCBSGCB
DystroglycanDystroglycan
DTNBDTNB
DTNADTNA
PGM5PGM5
Nonsense mutationNonsense mutation
Human artificial chromosomeHuman artificial chromosome
Muscular dystrophyMuscular dystrophy
SarcospanSarcospan
UtrophinUtrophin
YAP1YAP1
SNTB1SNTB1
MorpholinoMorpholino
Myoclonic dystoniaMyoclonic dystonia
SGCASGCA
DPYSL2DPYSL2
Viral cardiomyopathyViral cardiomyopathy
Delta-sarcoglycanDelta-sarcoglycan
SGCGSGCG
MACF1MACF1
Coxsackievirus-induced cardiomyopathyCoxsackievirus-induced cardiomyopathy
Ischemia-reperfusion injury of the appendicular musculoskeletal systemIschemia-reperfusion injury of the appendicular musculoskeletal system
Exon skippingExon skipping
MeganucleaseMeganuclease
Louis M. KunkelLouis M. Kunkel
Syntrophin, alpha 1Syntrophin, alpha 1
Lanthanide probesLanthanide probes
OrganismsDiseasesChemicals and DrugsPhenomena and ProcessesInformation Science
DystrophinMuscular Dystrophy, DuchenneAlgorithmsMuscular DystrophiesHominidaeMice, Inbred mdxUtrophin
DMD - Dystrophin - Homo sapiens (Human) - DMD gene & proteinDMD - Dystrophin - Homo sapiens (Human) - DMD gene & protein
Local and distant transfection of mdx muscle fibers with dystrophin and LacZ genes delivered in vivo by synthetic microspheres ...Local and distant transfection of mdx muscle fibers with dystrophin and LacZ genes delivered in vivo by synthetic microspheres ...
Dystrophin Dp71 Is Critical for the Clustered Localization of Potassium Channels in Retinal Glial Cells | Journal of...Dystrophin Dp71 Is Critical for the Clustered Localization of Potassium Channels in Retinal Glial Cells | Journal of...
Abstract 3808: AAV-9 Micro-Dystrophin Gene Therapy Halts Heart Disease Progression in Symptomatic Dystrophic Mice | CirculationAbstract 3808: AAV-9 Micro-Dystrophin Gene Therapy Halts Heart Disease Progression in Symptomatic Dystrophic Mice | Circulation
U-Ms gutted virus delivers dystrophin to muscles of adult mice with muscular dystrophyU-M's 'gutted virus' delivers dystrophin to muscles of adult mice with muscular dystrophy
Exon Skipping and Dystrophin Induction in Cardiac Muscle - Muscular DystrophyExon Skipping and Dystrophin Induction in Cardiac Muscle - Muscular Dystrophy
Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy | Science Translational...Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy | Science Translational...
Direct visualization of the dystrophin network on skeletal muscle fiber membrane. | Journal of Cell Biology | Rockefeller...Direct visualization of the dystrophin network on skeletal muscle fiber membrane. | Journal of Cell Biology | Rockefeller...
dystrophin proteindystrophin protein
Diagnostic strategy for the detection of dystrophin gene mutations in Asian patients and carriers using immortalized cell lines...Diagnostic strategy for the detection of dystrophin gene mutations in Asian patients and carriers using immortalized cell lines...
Brain dystrophin, neurogenetics and mental retardation<...Brain dystrophin, neurogenetics and mental retardation<...
Dystrophin Antibody (MANDRA1(7A10)) - DSHBDystrophin Antibody (MANDRA1(7A10)) - DSHB
Anti-Dystrophin Antibody (Monoclonal, MANDYS8)Anti-Dystrophin Antibody (Monoclonal, MANDYS8)
Dystrophin deficiency exacerbates skeletal muscle pathology in dysferlin-null mice | Skeletal Muscle | Full TextDystrophin deficiency exacerbates skeletal muscle pathology in dysferlin-null mice | Skeletal Muscle | Full Text
BIOETYMOLOGY : ORIGIN IN BIOMEDICAL TERMS: dystrophinBIOETYMOLOGY : ORIGIN IN BIOMEDICAL TERMS: dystrophin
Dystrophin - WikipediaDystrophin - Wikipedia
Dystrophin-associated protein - WikipediaDystrophin-associated protein - Wikipedia
Increasing complexity of the dystrophin-associated protein complex | PNASIncreasing complexity of the dystrophin-associated protein complex | PNAS
Dystrophin and mutations: one gene, several proteins, multiple phenotypes. - PubMed - NCBIDystrophin and mutations: one gene, several proteins, multiple phenotypes. - PubMed - NCBI
Low dystrophin levels are insuffi... preview & related info | MendeleyLow dystrophin levels are insuffi... preview & related info | Mendeley
The structural and functional diversity of dystrophinThe structural and functional diversity of dystrophin
Anti-Dystrophin antibody (ab15277) | AbcamAnti-Dystrophin antibody (ab15277) | Abcam
Analysis of Dystrophin Gene Deletions by Multiplex PCR in Moroccan PatientsAnalysis of Dystrophin Gene Deletions by Multiplex PCR in Moroccan Patients
Dystrophin | Disease Models & MechanismsDystrophin | Disease Models & Mechanisms
Image of the Day: Dystrophin Restored | The Scientist Magazine®Image of the Day: Dystrophin Restored | The Scientist Magazine®
dystrophin (human)dystrophin (human)
Increased neointimal thickening in dystrophin-deficient mdx mice. | Sigma-AldrichIncreased neointimal thickening in dystrophin-deficient mdx mice. | Sigma-Aldrich
Dystrophin: from non-ischemic cardiomyopathy to ischemic cardiomyopathy.Dystrophin: from non-ischemic cardiomyopathy to ischemic cardiomyopathy.
Exon Exchange Approach to Repair Duchenne Dystrophin TranscriptsExon Exchange Approach to Repair Duchenne Dystrophin Transcripts
Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials. - PubMed -...Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials. - PubMed -...
Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophyUtrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy
Dystrophin Summary Report | CureHunterDystrophin Summary Report | CureHunter
Functional protection of dystrophic mouse (mdx) muscles after adenovirus-mediated transfer of a dystrophin minigene | PNASFunctional protection of dystrophic mouse (mdx) muscles after adenovirus-mediated transfer of a dystrophin minigene | PNAS
Dystrophin is a microtubule-associated protein | JCBDystrophin is a microtubule-associated protein | JCB
sarcoglycan, alpha (50kDa dystrophin-associated glycoprotein) ELISA Kits | Biocompare.comsarcoglycan, alpha (50kDa dystrophin-associated glycoprotein) ELISA Kits | Biocompare.com
Fukutin-related protein associates with the sarcolemmal dystrophin-glycoprotein complex.Fukutin-related protein associates with the sarcolemmal dystrophin-glycoprotein complex.
Dystrophin Antibody (12715-1-AP) Dystrophin Antibody (12715-1-AP)
Exon-skipping drug prevents muscle wasting, maintains muscle function in dystrophin deficient mice - ScienceBlog.comExon-skipping drug prevents muscle wasting, maintains muscle function in dystrophin deficient mice - ScienceBlog.com
Gene Therapy Reveals Unexpected Immunity to Dystrophin in Patients with Duchenne Muscular DystrophyGene Therapy Reveals Unexpected Immunity to Dystrophin in Patients with Duchenne Muscular Dystrophy
Dystrophin gene abnormalities in two patients with idiopathic dilated cardiomyopathy | HeartDystrophin gene abnormalities in two patients with idiopathic dilated cardiomyopathy | Heart
Dystrophin (DMD) - Pipeline Review, H1 2018Dystrophin (DMD) - Pipeline Review, H1 2018
WikiGenes - SGCG - sarcoglycan, gamma (35kDa dystrophin...WikiGenes - SGCG - sarcoglycan, gamma (35kDa dystrophin...
Dystrophin (DMD) - Pipeline Review, H2 2016Dystrophin (DMD) - Pipeline Review, H2 2016
Discovery of new form of dystrophin protein could lead to therapy for some DMD patients | EurekAlert! Science NewsDiscovery of new form of dystrophin protein could lead to therapy for some DMD patients | EurekAlert! Science News
OrganismsDiseasesChemicals and DrugsPhenomena and ProcessesInformation Science
DystrophinMuscular Dystrophy, DuchenneAlgorithmsMuscular DystrophiesHominidaeMice, Inbred mdxUtrophin
Duchenne MuscularMiceNormal dystrophinCaused by mutationsFunctionalProteinsSarcolemmalProtein dystrophinCytoskeletonGlycoprotein complexDystrophicMuscleAbsenceExpressionRestorationDeficiencyMusclesAntibodyFragmentAdultGene productFunctionFibersMutationsProteinsSkeletalHuman dystrophinLoss of dystrophinFunction of dystrophinIsoformsUtrophinFull-length dystrophinSarcolemmaSarcoglycanDystroglycanExonsMembraneAntibodyCorrected dystrophin proteinBeckerMusclesDefectsDilated cardiomyopathySuggest that dystrophinProduction of dystrophinGeneticDeficientEncodes dystrophinNeuromuscularCytoplasmicCDNAMicro-dystrophin gene therapyEncoding the dystrophin proteinProtein complexRestoreGenes2018AbnormalitiesActin
Duchenne Muscular3
Mice10
  • Patterns of dystrophin and β-galactosidase expression were examined in mdx mice after i.m. injections of synthetic microspheres (MF-2) loaded with full-length (pHSADy) or mini-dystrophin gene (pSG5dys) cDNA plasmid constructs or with LacZ marker gene (pCMV-LacZ). (nature.com)
  • We report here for the first time efficient transfection of mdx mice myofibers with dystrophin gene constructs delivered in vivo by the microsphere particles MF-2. (nature.com)
  • The levels of dystrophin gene expression in different skeletal muscles as a function of time was examined in mdx mice after a single i.m. administration of microspheres loaded with 25 μg of full-length dystrophin cDNA (MF2/pHSADy). (nature.com)
  • Consistently, only minimum amount of dystrophin expression can be detected in the cardiac muscle even after repeated injections of both 2OMePS AON and PMO in all mdx mice aged 6 months or younger (Lu et al. (fitness-vip.com)
  • Because dysferlin and dystrophin play different roles in maintaining muscle cell integrity, we hypothesized that disrupting sarcolemmal integrity with dystrophin deficiency would exacerbate the pathology in dysferlin-null mice and allow further characterization of the role of dysferlin in skeletal muscle. (biomedcentral.com)
  • To test our hypothesis, we generated dystrophin/dysferlin double-knockout (DKO) mice by breeding mdx mice with dysferlin-null mice and analyzed the effects of a combined deficiency of dysferlin and dystrophin on muscle pathology and sarcolemmal integrity. (biomedcentral.com)
  • Dystrophin/dysferlin-deficient mice provide a very useful model with which to evaluate the effectiveness of therapies designed to treat dysferlin deficiency. (biomedcentral.com)
  • In DMD patients and mdx mice, which also have a mutation in the dystrophin gene, loss of dystrophin disrupts the link between the cytoskeleton and the ECM, leading to the loss of sarcolemmal integrity. (biomedcentral.com)
  • The treated mice show persistent production of dystrophin at normal levels in large numbers of muscle fibers and show functional improvement of the treated muscle. (qxmd.com)
  • At 90 days post-transplant, dystrophin expression in cardiac muscles of DEC injected mice significantly increased (15.73% ± 5.70 -MB wt /MB mdx and 5.22% ± 1.10 - MB wt /MSC mdx DEC) when compared to vehicle injected controls (2.01% ± 1.36) and, correlated with improved ejection fraction and fractional shortening on echocardiography. (springer.com)
Normal dystrophin1
Caused by mutations1
Functional7
  • Dystrophin is a complex plasmalemmal-cytoskeletal linker protein that possesses multiple functional domains, autosomal and X-linked homologs and associated binding proteins that form multiunit signaling complexes whose composition is unique to each cellular and developmental context. (elsevier.com)
  • In DMD/BMD, the individual profiles of cognitive and behavioral deficits, mental retardation and other phenotypic variations appear to depend on complex profiles of transcriptional regulation associated with individual dystrophin mutations that result in the corresponding presence or absence of individual brain dystrophin isoforms that normally exhibit developmental, regional and cell-type-specific expression and functional regulation. (elsevier.com)
  • Thus, splicing around mutations can generate a shortened but in-frame transcript, permitting translation of a partially functional dystrophin protein. (qxmd.com)
  • We previously reported functional improvements correlating with dystrophin restoration following transplantation of Dystrophin Expressing Chimeric Cells (DEC) of myoblast origin in the mdx and mdx/scid mouse models. (springer.com)
  • Eteplirsen is a morpholino antisense oligomer that triggers the excision of the out-of-frame exon 51 during the pre-mRNA splicing of the dystrophin RNA transcript, leading to the production of truncated, yet functional dystrophin. (biovox.eu)
  • Solid Biosciences is preparing an initial clinical trial for an AAV-based therapy that delivers a shortened, yet functional version of dystrophin) and gene editing therapy (e.g. (biovox.eu)
  • The key challenge with these ongoing approaches will be to impact a sufficiently high fraction of the muscle cells and to supply enough functional dystrophin to restore muscle function. (biovox.eu)
Proteins4
  • Therefore, connection of defined areas of plasma membrane or its constituents such as ion channels to single sarcomeres might be a potential function exerted by dystrophin alone or in conjunction with other submembrane cytoskeletal proteins. (rupress.org)
  • Through additional interactions with a variety of proteins of the extracellular matrix, plasma membrane, cytoskeleton and distinct intracellular compartments, brain dystrophin acquires the capability to participate in the modulatory actions of a large number of cellular signaling pathways. (elsevier.com)
  • Dystrophin is a vital structural link between the extracellular matrix and the cytoskeletal proteins and plays an essential role in several important biochemical extracellular signaling pathways. (springer.com)
  • In skeletal muscle, there are a few known PDZ-domain proteins, which include neuronal nitric oxide synthase and syntrophin, both of which are components of the dystrophin complex, and actinin-associated LIM protein, which binds to the spectrin-like repeats of alpha-actinin-2. (unipd.it)
Sarcolemmal1
Protein dystrophin1
Cytoskeleton2
  • Dystrophin links the cytoskeleton to the sarcolemma through direct interaction with β-dystroglycan. (biomedcentral.com)
  • Dystrophin plays an important role in linking the cytoskeleton to the sarcolemma through the direct interactions of its N-terminus with F-actin and its C-terminus with β-dystroglycan [ 2 ]. (biomedcentral.com)
Glycoprotein complex3
  • Component of the dystrophin- associated glycoprotein complex which accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems and has a structural function in stabilizing the sarcolemma. (bosterbio.com)
  • However, the rate of force recovery within 45 minutes following lengthening contractions was hampered in DKO muscles compared to mdx muscles or dysferlin-null muscles, suggesting that dysferlin is required for the initial recovery from lengthening contraction-induced muscle injury of the dystrophin-glycoprotein complex-compromised muscles. (biomedcentral.com)
  • Dystrophin is an integral component of the dystrophin-glycoprotein complex (DGC) and is localized to the inner surface of the plasma membrane [ 2 ]. (biomedcentral.com)
Dystrophic1
Muscle10
  • Direct visualization of the dystrophin network on skeletal muscle fiber membrane. (rupress.org)
  • We have shown that dystrophin molecules are not uniformly distributed over the humen, rat, and mouse skeletal muscle fiber surface using three independent methods. (rupress.org)
  • Incubation of single-teased muscle fibers with antibodies to dystrophin revealed a network of denser transversal rings (costameres) and finer longitudinal interconnections. (rupress.org)
  • Mechanical skinning of single-teased fibers revealed tighter mechanical connection of dystrophin to the plasma membrane than to the underlying internal domain of the muscle fiber. (rupress.org)
  • The entire dystrophin network remained preserved in its structure on isolated muscle sarcolemma and identical in appearance to the pattern observed on teased fibers. (rupress.org)
  • Dystrophin deficiency clinically manifests as skeletal and cardiac muscle weakness, leading to muscle wasting and premature death due to cardiac and respiratory failure. (springer.com)
  • PF-06939926 is an investigational gene transfer therapy intended to deliver its mini-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein. (medicalbiochemist.com)
  • AAV9.Muscle-promoter.micro-dystrophin). (medicalbiochemist.com)
  • AAV9.MuscleProtomter.mini-dystrophin (3.9Kb), The propriety muscle promoter drives the expression of the minidystrophin gene in the muscle tissue. (medicalbiochemist.com)
  • The Phase 1b study conducted to determine the safety and tolerability of the AAV9.Muscle-promoter.micro-dystrophin is completed and one year data is provided in the ASGCT Investor call. (medicalbiochemist.com)
Absence2
  • The absence of any efficient pharmaceutical or biological (myoblast transplantation) methods for the treatment of DMD makes the development of gene therapy approaches for widespread systemic delivery of dystrophin gene to skeletal muscles very urgent for the correction and management of this primary lethal genetic disorder. (nature.com)
  • Out-of-frame mutations in DMD lead to absence of the dystrophin protein, while in-frame BMD mutations cause production of internally deleted dystrophin. (bmj.com)
Expression3
Restoration1
Deficiency2
  • Dystrophin deficiency in DMD/BMD patients and in the mdx mouse model appears to impair intracellular calcium homeostasis and to disrupt multiple protein-protein interactions that normally promote information transfer and signal integration from the extracellular environment to the nucleus within regulated microdomains. (elsevier.com)
  • Dystrophin deficiency unmasks the function of dysferlin in membrane repair during lengthening contractions. (biomedcentral.com)
Muscles4
  • MF-2/dystrophin cDNA par- ticles were detected by FISH analysis in about 60-70% of myofiber nuclei in muscles of injected and contralateral limbs 7 days after application. (nature.com)
  • The presence of human dystrophin cDNA and its products in all skeletal muscles and in different internal organs was proven by PCR and RT-PCR analysis. (nature.com)
  • 2006), whereas the same treatment can induce high levels of dystrophin in skeletal muscles. (fitness-vip.com)
  • However, direct injection of AON into cardiac muscles showed effective dystrophin induction, suggesting that lower delivery efficiency is perhaps the most critical factor (Vitiello et al. (fitness-vip.com)
Antibody1
Fragment1
Adult1
  • Increasing experimental evidence suggests that in adult life, dystrophin normally modulates synaptic terminal integrity, distinct forms of synaptic plasticity and regional cellular signal integration. (elsevier.com)
Gene product1
  • Seven promoters scattered throughout the huge DMD/BMD gene locus normally code for distinct isoforms of the gene product, dystrophin, that exhibit nervous system developmental, regional and cell-type specificity. (elsevier.com)
Function1
Fibers1
  • 1, 2 Myofibers lacking dystrophin are abnormally susceptible to contraction-induced sarcolemma damage with subsequent myofiber dysfunction, necrosis and regeneration leading ultimately to the replacement of the lost fibers by adipose and connective tissue and premature death often associated with cardiomyopathy. (nature.com)
Mutations35
Proteins30
  • Dystrophin and its associated proteins form a scaffold underneath the cardiomyocyte membrane and connect the intracellular cytoskeleton to the extracellular matrix. (biomedsearch.com)
  • It shares features with other cytoskeletal proteins such as SPECTRIN and alpha-actinin but the precise function of dystrophin is not clear. (curehunter.com)
  • Videos accompanying the online publication show visual evidence of pronounced curving of the spine and dramatically reduced mobility as a result of deficiency of both dystrophin and utrophin proteins (Hyperlink to: Mouse Pretreatment/Supplementary Video S1, http://www.avibio.com/videos03.php ). (scienceblog.com)
  • A macromolecular complex of proteins that includes DYSTROPHIN and DYSTROPHIN-ASSOCIATED PROTEINS. (curehunter.com)
  • Dystrophin and its partially redundant homolog Utrophin are associated with a number of other proteins, members of the Dystrophin-glycoprotein complex (DGC) ( Ervasti and Campbell, 1991 ). (jneurosci.org)
  • Dystrophins and dystrobrevins are distantly related proteins with important but poorly understood roles in the function of metazoan muscular and neuronal tissues. (biomedcentral.com)
  • PURPOSE: To test the hypothesis that exercise training (ET) would alleviate age-related disruption of localization in DGC proteins (dystrophin, α-syntrophin, and β-sarcoglycan), and ET will upregulate decorin. (wku.edu)
  • Dystrophin localizes to the sarcolemma and stabilizes a complex of proteins (dystrophin-associated proteins, DAPs) that link the extracellular matrix to the actin cytoskeleton ( Ohlendieck, 1996 ). (biologists.org)
  • Several studies have shown that α-dystrobrevin can bind many of the same proteins that associate with dystrophin. (biologists.org)
  • an adapter protein that links signaling proteins to the dystrophin-dystrobrevin scaffold. (biologists.org)
  • Therefore, both dystrophin and dystrobrevin serve as scaffolds for a variety of signaling proteins. (biologists.org)
  • Dystrophin-less DMD and MDX myotubes were more susceptible to hypoosmotic shock than controls, as monitored by the uptake of external horseradish peroxidase and release of the soluble enzymes creatinine kinase or pyruvate kinase and of radiolabelled proteins. (biologists.org)
  • The present study was intended to identify all known members of the dystrophin superfamily and their associated proteins expressed in Müller glial cells (MGC). (arvojournals.org)
  • In morphologically preserved differentiated Müller cells, Dp71f was localized in clusters, utrophin was diffusely distributed in the cytoplasm, and dystrophin-associated proteins (DAPs) were membrane-bound. (arvojournals.org)
  • 1 In the muscle, dystrophin is a submembranous cytoskeletal protein 2 that links actin 3 to a complex of dystrophin-associated proteins (DAPs) composed of transmembranous and submembranous proteins, such as dystroglycans, sarcoglycans, and syntrophins. (arvojournals.org)
  • Utrophin and dystrophins are minor actin-binding proteins present in muscle and non-muscle cytoskeleton. (inserm.fr)
  • Two new dystrophin isoforms were found, Dp71f and Dp71 d, as well as the Up71 isoform and the dystrophin-associated proteins, alpha and beta -dystrobrevins. (inserm.fr)
  • Distribution of Dp71d/Dp71delta110m, Up400/Up71 and dystrophin-associated proteins in relation to the actin cytoskeleton was evaluated by confocal microscopy in both resting and platelets adhered on glass. (inserm.fr)
  • Therefore, connection of defined areas of plasma membrane or its constituents such as ion channels to single sarcomeres might be a potential function exerted by dystrophin alone or in conjunction with other submembrane cytoskeletal proteins. (rupress.org)
  • In skeletal muscle, dystrophin is associated with a large, oligomeric complex of proteins that includes dystroglycans, sarcoglycans, dystrobrevins, syntrophins and sarcospan ( Straub and Campbell 1997 ). (rupress.org)
  • Of the numerous elements necessary for proper functioning of this synaptic contact, dystrophin proteins in the eye play an important role. (arvojournals.org)
  • Dystrophin is a complex plasmalemmal-cytoskeletal linker protein that possesses multiple functional domains, autosomal and X-linked homologs and associated binding proteins that form multiunit signaling complexes whose composition is unique to each cellular and developmental context. (elsevier.com)
  • Through additional interactions with a variety of proteins of the extracellular matrix, plasma membrane, cytoskeleton and distinct intracellular compartments, brain dystrophin acquires the capability to participate in the modulatory actions of a large number of cellular signaling pathways. (elsevier.com)
  • Members of the dystrophin family of proteins perform a critical role in the maintenance of membrane-associated complexes at points of intercellular contact in vertebrate cells. (nih.gov)
  • Association of syncollin and desmin: Linking intermediate filament proteins to the dystrophin-associated protein complex. (ox.ac.uk)
  • A group of proteins including dystrophin bound together which form a critical link between the inside and outside of muscle cells. (musculardystrophyuk.org)
  • The absence of dystrophin leads to a dramatic reduction of the dystrophin-associated proteins (156DAG, 59DAP, 50DAG, 43DAG and 35DAG) in the sarcolemma of patients with Duchenne muscular dystrophy and mdx mice 2,6-8 . (umn.edu)
  • Here we demonstrate that dystrophin-related protein (DRP, utrophin), an autosomal homologue of dystrophin 9,17 , is associated with an identical or antigenically similar complex of sarcolemmal proteins and that DRP and the dystrophin/DRP-associated proteins colocalize to the neuromuscular junction in Duchenne muscular dystrophy and mdx muscle. (umn.edu)
  • The DRP and dystrophin/DRP-associated proteins are found throughout the sarcolemma in small-calibre skeletal muscles and cardiac muscle of adult mdx mice. (umn.edu)
  • The dystrophin-glycoprotein complex (DGC) comprises a group of proteins that are critical to the stability of muscle fiber membranes and to the linking of the actin cytoskeleton to the extracellular matrix. (wikipedia.org)
Skeletal27
Human dystrophin3
Loss of dystrophin3
Function of dystrophin4
Isoforms7
Utrophin4
Full-length dystrophin7
Sarcolemma15
  • Dystrophin is a protein located between the sarcolemma and the outermost layer of myofilaments in the muscle fiber (myofiber). (wikipedia.org)
  • Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems and has a structural function in stabilizing the sarcolemma. (abcam.com)
  • 1, 2 Myofibers lacking dystrophin are abnormally susceptible to contraction-induced sarcolemma damage with subsequent myofiber dysfunction, necrosis and regeneration leading ultimately to the replacement of the lost fibers by adipose and connective tissue and premature death often associated with cardiomyopathy. (nature.com)
  • The absence of dystrophin at the sarcolemma also delocalizes and downregulates nitric oxide synthase (nNOS) and alters enzymatic antioxidant responses, leading to an increase in oxidative stress. (mdpi.com)
  • These results position archvillin (zeige SVIL Antikörper ) as a mechanically sensitive component of the dystrophin (zeige DMD Antikörper ) complex and demonstrate that signaling defects caused by loss of gamma-SG occur both at the sarcolemma and in the nucleus. (antikoerper-online.de)
  • Despite restoration of sarcolemmal α-syntrophin, neuronal nitric oxide synthase (nNOS) was not localized to the sarcolemma, suggesting that nNOS requires both dystrophin and α-syntrophin for correct localization. (biologists.org)
  • It is α-dystrobrevin-2a that is most abundant on the sarcolemma where it colocalizes with dystrophin. (biologists.org)
  • We have demonstrated gene therapy with this vector by restoring dystrophin expression in DMD myoblasts, where dystrophin was expressed at the sarcolemma of myotubes after myogenic differentiation. (physiciansweekly.com)
  • The entire dystrophin network remained preserved in its structure on isolated muscle sarcolemma and identical in appearance to the pattern observed on teased fibers. (rupress.org)
  • A population of γ-actin filaments was stably associated with sarcolemma isolated from normal muscle and displayed a costameric pattern that precisely overlapped with dystrophin. (rupress.org)
  • However, costameric actin was absent from all sarcolemma isolated from dystrophin-deficient mdx mouse muscle even though it was localized to costameres in situ. (rupress.org)
  • Our data demonstrate that the dystrophin complex forms a mechanically strong link between the sarcolemma and the costameric cytoskeleton through interaction with γ-actin filaments. (rupress.org)
  • Dystrophin labelling in equatorial regions of normal intrafusal fibers, however, showed dystrophin-deficient segments alternating in a spiral fashion with positive-staining domains along the sarcolemma. (ubc.ca)
  • Dystrophin links the cytoskeleton to the sarcolemma through direct interaction with β-dystroglycan. (biomedcentral.com)
  • Dystrophin plays an important role in linking the cytoskeleton to the sarcolemma through the direct interactions of its N-terminus with F-actin and its C-terminus with β-dystroglycan [ 2 ]. (biomedcentral.com)
Sarcoglycan8
Dystroglycan5
Exons1
Membrane8
  • Moreover, we hypothesize that dystrophin play a critical role in ventricular remodeling in ischemic myocardium and treatment targeting restoration of dystrophin onto membrane could benefit for ischemic cardiomyopathy. (biomedsearch.com)
  • The absence of dystrophin leads to myofiber membrane fragility that results in the progressive muscular degeneration that characterizes DMD ( Sussman, 2002 ). (frontiersin.org)
  • Most of the dystrophin protein consists of a central domain made of 24 spectrin-like coiled-coil repeats (R). Using small angle neutron scattering (SANS) and the contrast variation technique, we specifically probed the structure of the three first consecutive repeats 1-3 (R1-3), a part of dystrophin known to physiologically interact with membrane lipids. (cea.fr)
  • Dystrophin maintains the integrity of striated muscles by linking the actin cytoskeleton with the cell membrane. (jci.org)
  • The dystrophin-glycoprotein complex (DGC) is localized and integrated into the cell membrane. (wku.edu)
  • These results lend further support to the suggested stabilizing role of dystrophin in the context of the membrane-cytoskeletal complex. (biologists.org)
  • The results of this study suggest that dystrophin is not an integral part of the subsynaptic sensory-membrane in equatorial regions of normal intrafusal fibers, and, that the neurotrophic effect of sensory innervation is not the principle cause of this unique arrangement of dystrophin in equatorial regions. (ubc.ca)
  • Dystrophin is an integral component of the dystrophin-glycoprotein complex (DGC) and is localized to the inner surface of the plasma membrane [ 2 ]. (biomedcentral.com)
Antibody6
  • The following antibody was used in this experiment: Dystrophin Polyclonal Antibody from Thermo Fisher Scientific, catalog # 12715-1-AP. (thermofisher.com)
  • Cultures containing dystrophic myoblasts were seeded in 8 well chambers and were targeted with a 72 hour recovery time after the addition of the either the nonspecific ODN (A) or mdx47NT (B). These cells were then allowed to differentiate for 96 hours at which point they were fixed and incubated with antibody specific for a rabbit polyclonal antibody that recognizes dystrophin and a secondary Alexa fluor labeled antibody (red). (nih.gov)
  • The entire assay was performed in microscope chambers so that the samples could be probed directly with an antibody specific for the dystrophin protein. (nih.gov)
  • Transduction efficiency was assessed by immuno-staining using an antibody (Manex1a) that recognizes the N-terminus of micro-dystrophin. (biomedcentral.com)
  • Spindles were serially-sectioned in transverse and longitudinal planes, and they were double-labelled with an antibody to dystrophin and with a 200 kD neurofilament protein antibody which revealed their sensory innervation. (ubc.ca)
  • Mouse IgG monoclonal antibody for Dystrophin, dystrophin (DMD) detection. (bosterbio.com)
Corrected dystrophin protein2
Becker12
Muscles7
  • Results from a Phase 1 proof-of-concept trial showed that injection of the drug into the muscles of a series of boys with DMD successfully induced dystrophin production in a dose-responsive manner. (scienceblog.com)
  • MF-2/dystrophin cDNA par- ticles were detected by FISH analysis in about 60-70% of myofiber nuclei in muscles of injected and contralateral limbs 7 days after application. (nature.com)
  • However, direct injection of AON into cardiac muscles showed effective dystrophin induction, suggesting that lower delivery efficiency is perhaps the most critical factor (Vitiello et al. (fitness-vip.com)
  • 2008). This is further supported by the restoration of dystrophin in cardiac muscles via AAV-mediated AON delivery (Denti et al. (fitness-vip.com)
  • Immunoblotting of dystrophin in DMD muscles reveals the total absence of dystrophin except in some revertant fibers. (thefreedictionary.com)
  • The latter study showed that it is possible to correct the genetic error in the cells that no longer produce dystrophin protein, and inject corrected cells stimulating the regeneration of muscles. (stemcellsgroup.com)
  • It is caused by a mutation in the DMD gene that carries the instruction to make dystrophin, the protein that provides structural support and protection to the muscles. (musculardystrophynews.com)
Defects2
Dilated cardiomyopathy3
Suggest that dystrophin1
  • Recent studies suggest that dystrophin may contain unique domains that can help the heart better cope with the stress generated during contraction. (pharmiweb.com)
Production of dystrophin2
  • In this study, the researchers found that equal parts enzyme and guide RNA-targeted at a specific part of the DMD gene-didn't bump up the production of dystrophin very much. (the-scientist.com)
  • However, when the patients were evaluated three months later, long-term production of dystrophin protein from the corrected DMD gene was not detected. (nationwidechildrens.org)
Genetic7
  • Genetic, biochemical and anatomical studies of dystrophin suggest that a number of distinct functions are subserved by its great structural diversity. (nih.gov)
  • Dystrophin abnormalities are thought to occur in 100% of patients with DMD/BMD, although genetic abnormalities may only be detected in up to 65% of cases. (thermofisher.com)
  • A novel stress syndrome was characterized in pigs and the causative genetic factor most likely resides within DMD that results in less dystrophin protein and cardiac abnormalities that can lead to death under stressful conditions. (biomedcentral.com)
  • The secret: an ordinary virus with all its natural genetic material removed to make room for the dystrophin gene which triggers production of the protein. (umich.edu)
  • In this study, we aim to knockdown myostatin by means of exon skipping, a technique which has been successfully applied to reframe the genetic defect of dystrophin gene in DMD patients. (springer.com)
  • The proteoglycan-dystrophin complex in genetic cardiomyopathie. (mysciencework.com)
  • The proteoglycan-dystrophin complex in genetic cardiomyopathies--lessons from three siblings with limb-girdle muscular dystrophy-2I (LGMD-2I). (mysciencework.com)
Deficient3
  • parallels the structural deficiencies observed in other cytolinker-deficient tissues, further demonstrating a close relationship between dystrophin and other cytolinkers. (rupress.org)
  • The dystrophin-deficient mdx mouse has historically been used as the primary model of DMD, although this mouse does not experience the severe, body-wide dystrophy that considerably shortens lifespan in humans. (scienceblog.com)
  • Double-labelling for dystrophin and neurofilament protein showed that these dystrophin-deficient sites were subjacent to the annulospiral sensory-nerve wrappings terminating on the intrafusal fibers. (ubc.ca)
Encodes dystrophin1
  • A large and complex gene on the X chromosome encodes dystrophin. (nih.gov)
Neuromuscular1
Cytoplasmic1
CDNA1
  • The capacity of AAV1, AAV6 or AAV8 to cross the vascular endothelial barrier carrying a micro-dystrophin cDNA was compared under identical conditions with delivery through a catheter placed in the femoral artery of the mdx mouse. (biomedcentral.com)
Micro-dystrophin gene therapy2
Encoding the dystrophin protein1
Protein complex2
Restore1
  • Subsequent clinical trials have shown that two different AON chemistries, either 2'- O -methyl phosphorothioate (2'OMePS)[ 12 ] or phosphorodiamidate morpholino oligomer (PMO)[ 13 ] targeting DMD exon 51 can restore local dystrophin synthesis in DMD patients with no to minimum side effect. (springer.com)
Genes3
  • Stripping away genes normally found in the virus not only frees up enough space for a full-sized version of dystrophin, it also may make it possible to avoid triggering the body's immune system, according to Chamberlain. (umich.edu)
  • Furthermore, combination of myostatin and dystrophin AONs induced simultaneous skipping of both genes. (springer.com)
  • In this study, we will dissect the role(s) these domains play in the heart, and more importantly, we will develop next-generation micro-dystrophin genes to more effectively protect the heart. (pharmiweb.com)
20182
  • The latest report Dystrophin (DMD) - Pipeline Review, H1 2018, outlays comprehensive information on the Dystrophin (DMD) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (marketresearch.com)
  • Independently, we will also request a meeting with the Agency to discuss the micro-dystrophin program with the goal of commencing a pivotal trial by year-end 2018. (firstwordpharma.com)
Abnormalities1
  • We have analyzed DNA from 72 Moroccan patients with DMD/BMD using the multiplex polymerase chain reaction (PCR) to screen for exon deletions within the dystrophin gene, and to estimate the frequency of these abnormalities. (hindawi.com)
Actin1
  • Formation of two dystrophin-associated protein complexes (Dp71d/Dp71delta110m approximately DAPC and Up400/Up71 approximately DAPC) was demonstrated by co-immunoprecipitation and their distribution in relation to the actin cytoskeleton was characterised during platelet adhesion. (inserm.fr)
Local and distant transfection of mdx muscle fibers with dystrophin and LacZ genes delivered in vivo by synthetic microspheres ...
Local and distant transfection of mdx muscle fibers with dystrophin and LacZ genes delivered in vivo by synthetic microspheres ... (nature.com)
Dystrophin is a component of the subsynaptic membrane. | JCB
Dystrophin is a component of the subsynaptic membrane. | JCB (jcb.rupress.org)
Clinical characterisation of Becker muscular dystrophy patients predicts favourable outcome in exon-skipping therapy | Journal...
Clinical characterisation of Becker muscular dystrophy patients predicts favourable outcome in exon-skipping therapy | Journal... (jnnp.bmj.com)
The subcellular distribution of chromosome 6-encoded dystrophin-related protein in the brain. | JCB
The subcellular distribution of chromosome 6-encoded dystrophin-related protein in the brain. | JCB (jcb.rupress.org)
Exon Skipping and Dystrophin Induction in Cardiac Muscle - Muscular Dystrophy
Exon Skipping and Dystrophin Induction in Cardiac Muscle - Muscular Dystrophy (fitness-vip.com)
Exon Exchange Approach to Repair Duchenne Dystrophin Transcripts
Exon Exchange Approach to Repair Duchenne Dystrophin Transcripts (journals.plos.org)
Increasing complexity of the dystrophin-associated protein complex | PNAS
Increasing complexity of the dystrophin-associated protein complex | PNAS (pnas.org)
Double-deficient mice clarify Duchenne muscular dystrophy DMD disease process
Double-deficient mice clarify Duchenne muscular dystrophy DMD disease process (jax.org)
Desmin - Wikipedia
Desmin - Wikipedia (en.wikipedia.org)
Duchenne Muscular Dystrophy (DMD) (Example) - MindMeister
Duchenne Muscular Dystrophy (DMD) (Example) - MindMeister (mindmeister.com)
Increased neointimal thickening in dystrophin-deficient mdx mice. | Sigma-Aldrich
Increased neointimal thickening in dystrophin-deficient mdx mice. | Sigma-Aldrich (sigmaaldrich.com)
MedlinePlus: Genes: D
MedlinePlus: Genes: D (medlineplus.gov)
Quest Landing | Muscular Dystrophy Association
Quest Landing | Muscular Dystrophy Association (mda.org)
What causes congenital muscular dystrophy (CMD) with familial junctional epidermolysis bullosa?
What causes congenital muscular dystrophy (CMD) with familial junctional epidermolysis bullosa? (medscape.com)
Functional protection of dystrophic mouse (mdx) muscles after adenovirus-mediated transfer of a dystrophin minigene | PNAS
Functional protection of dystrophic mouse (mdx) muscles after adenovirus-mediated transfer of a dystrophin minigene | PNAS (pnas.org)
Discovery of new form of dystrophin protein could lead to therapy for some DMD patients | EurekAlert! Science News
Discovery of new form of dystrophin protein could lead to therapy for some DMD patients | EurekAlert! Science News (eurekalert.org)
JPM | Free Full-Text | Multiple Exon Skipping in the Duchenne Muscular Dystrophy Hot Spots: Prospects and Challenges
JPM | Free Full-Text | Multiple Exon Skipping in the Duchenne Muscular Dystrophy Hot Spots: Prospects and Challenges (mdpi.com)
Extension Study of BMN 044 in Duchenne Muscular Dystrophy (DMD) - Full Text View - ClinicalTrials.gov
Extension Study of BMN 044 in Duchenne Muscular Dystrophy (DMD) - Full Text View - ClinicalTrials.gov (clinicaltrials.gov)
Dystrophin is a microtubule-associated protein | JCB
Dystrophin is a microtubule-associated protein | JCB (jcb.rupress.org)
Journal of Neuromuscular Diseases - Volume 3, issue 1 - Journals - IOS Press
Journal of Neuromuscular Diseases - Volume 3, issue 1 - Journals - IOS Press (content.iospress.com)
The zebrafish candyfloss mutant implicates extracellular matrix adhesion failure in laminin α2-deficient congenital muscular...
The zebrafish candyfloss mutant implicates extracellular matrix adhesion failure in laminin α2-deficient congenital muscular... (pnas.org)
Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer | PNAS
Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer | PNAS (pnas.org)
RCSB PDB - 1EG4: STRUCTURE OF A DYSTROPHIN WW DOMAIN FRAGMENT IN COMPLEX WITH A BETA-DYSTROGLYCAN PEPTIDE
RCSB PDB - 1EG4: STRUCTURE OF A DYSTROPHIN WW DOMAIN FRAGMENT IN COMPLEX WITH A BETA-DYSTROGLYCAN PEPTIDE (rcsb.org)
WikiGenes - SGCG - sarcoglycan, gamma (35kDa dystrophin...
WikiGenes - SGCG - sarcoglycan, gamma (35kDa dystrophin... (wikigenes.org)
JISCMail - ACB-CLIN-CHEM-GEN Archives - September 2015
JISCMail - ACB-CLIN-CHEM-GEN Archives - September 2015 (jiscmail.ac.uk)
All About Human Genetic Disorders
All About Human Genetic Disorders (brighthub.com)