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.
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)
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.
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.
Muscular Dystrophy, Animal refers to a group of inherited genetic disorders that cause progressive muscle weakness and wasting in animals.
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.
A group of proteins that associate with DYSTROPHIN at the CELL MEMBRANE to form the DYSTROPHIN-ASSOCIATED PROTEIN COMPLEX.
Dystrophin-associated proteins that play role in the formation of a transmembrane link between laminin-2 and DYSTROPHIN. Both the alpha and the beta subtypes of dystroglycan originate via POST-TRANSLATIONAL PROTEIN PROCESSING of a single precursor protein.
The excitable plasma membrane of a muscle cell. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
A family of transmembrane dystrophin-associated proteins that play a role in the membrane association of the DYSTROPHIN-ASSOCIATED PROTEIN COMPLEX.
A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.
A macromolecular complex of proteins that includes DYSTROPHIN and DYSTROPHIN-ASSOCIATED PROTEINS. It plays a structural role in the linking the CYTOSKELETON to the EXTRACELLULAR MATRIX.
Contractile tissue that produces movement in animals.
Synthetic analogs of NUCLEIC ACIDS composed of morpholine ring derivatives (MORPHOLINES) linked by phosphorodimidates. One standard DNA nucleic acid base (ADENINE; GUANINE; CYTOSINE; OR THYMINE) is bound to each morpholine ring.
The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.
Large, multinucleate single cells, either cylindrical or prismatic in shape, that form the basic unit of SKELETAL MUSCLE. They consist of MYOFIBRILS enclosed within and attached to the SARCOLEMMA. They are derived from the fusion of skeletal myoblasts (MYOBLASTS, SKELETAL) into a syncytium, followed by differentiation.
Short fragments of RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane.
Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.
A caveolin that is expressed exclusively in MUSCLE CELLS and is sufficient to form CAVEOLAE in SARCOLEMMA. Mutations in caveolin 3 are associated with multiple muscle diseases including DISTAL MYOPATHY and LIMB-GIRDLE MUSCULAR DYSTROPHY.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin.
A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.
The three possible sequences of CODONS by which GENETIC TRANSLATION may occur from one nucleotide sequence. A segment of mRNA 5'AUCCGA3' could be translated as 5'AUC.. or 5'UCC.. or 5'CCG.., depending on the location of the START CODON.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.

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)

Dystrophin is a protein that plays a crucial role in maintaining the structural integrity of muscle fibers in the human body. It is encoded by the DMD gene, which is located on the X chromosome. Dystrophin is responsible for linking the inner and outer layers of muscle fibers, providing them with stability and preventing them from tearing during muscle contraction. When the DMD gene is mutated or absent, dystrophin cannot be produced, leading to a deficiency in the protein. This deficiency is the underlying cause of Duchenne muscular dystrophy (DMD), a severe and progressive muscle-wasting disorder that primarily affects boys. DMD is characterized by muscle weakness and wasting, which can lead to difficulty walking, breathing, and even death in severe cases. In addition to DMD, dystrophin deficiency can also cause other forms of muscular dystrophy, such as Becker muscular dystrophy and dilated cardiomyopathy.

Duchenne Muscular Dystrophy (DMD) is a genetic disorder that affects muscle strength and function. It is caused by mutations in the dystrophin gene, which is responsible for producing a protein called dystrophin that helps to maintain the integrity of muscle fibers. Without dystrophin, muscle fibers become damaged and break down, leading to progressive muscle weakness and wasting. DMD primarily affects boys and is usually diagnosed in early childhood. The symptoms of DMD typically begin with difficulty in walking and running, which worsen over time. As the disease progresses, affected individuals may experience difficulty in climbing stairs, getting up from a seated position, and even breathing. The disease can also affect the heart and respiratory muscles, leading to serious complications. There is currently no cure for DMD, but there are treatments available that can help manage symptoms and improve quality of life. These may include physical therapy, assistive devices, and medications to help manage muscle stiffness and pain. In some cases, a heart transplant may be necessary to treat complications related to heart muscle damage.

Utrophin is a protein that is similar in structure to dystrophin, a protein that is essential for maintaining the integrity of muscle fibers. Dystrophin deficiency is the underlying cause of Duchenne muscular dystrophy (DMD), a severe and progressive muscle-wasting disorder that primarily affects boys. Utrophin is thought to play a compensatory role in DMD, as it is upregulated in muscle cells in response to dystrophin deficiency. However, utrophin is not as effective as dystrophin at maintaining muscle fiber integrity, and its overexpression can actually exacerbate muscle damage in some cases. In recent years, there has been significant research into the potential of utrophin as a therapeutic target for DMD. Some studies have shown that increasing utrophin expression in muscle cells can improve muscle function and reduce inflammation in animal models of the disease. However, more research is needed to determine the safety and efficacy of utrophin-based therapies in humans.

Muscular dystrophy is a group of genetic disorders that cause progressive muscle weakness and wasting. In animals, muscular dystrophy can occur in a variety of species, including dogs, cats, horses, and cattle. The symptoms of muscular dystrophy in animals can vary depending on the specific type of the disorder and the affected muscle groups. Common signs of muscular dystrophy in animals include muscle weakness, difficulty walking or moving, and a characteristic wobbly gait. In some cases, animals with muscular dystrophy may also experience muscle stiffness, muscle pain, and muscle spasms. Treatment for muscular dystrophy in animals typically involves managing the symptoms of the disorder and providing supportive care to improve the animal's quality of life.

Muscular dystrophies are a group of genetic disorders that cause progressive muscle weakness and wasting. These disorders are caused by mutations in genes that are responsible for producing proteins that are essential for maintaining the structure and function of muscle fibers. There are many different types of muscular dystrophies, each with its own specific genetic cause and pattern of inheritance. Some of the most common types of muscular dystrophy include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), facioscapulohumeral muscular dystrophy (FSHD), and myotonic dystrophy (DM). The symptoms of muscular dystrophy can vary widely depending on the type and severity of the disorder. Common symptoms include muscle weakness, difficulty with movement, muscle stiffness, and fatigue. In some cases, muscular dystrophy can also affect other organs, such as the heart and lungs. There is currently no cure for muscular dystrophy, but there are treatments available that can help manage symptoms and slow the progression of the disease. These may include physical therapy, medications, and assistive devices such as braces or wheelchairs.

Dystrophin-associated proteins (DAPs) are a group of proteins that interact with dystrophin, a protein that plays a critical role in maintaining the structural integrity of muscle fibers. Dystrophin is absent or mutated in Duchenne muscular dystrophy (DMD), a severe genetic disorder that causes progressive muscle weakness and wasting. DAPs include a variety of proteins that are essential for maintaining the stability of the dystrophin-glycoprotein complex (DGC), which is a large protein complex that spans the sarcolemma (the plasma membrane of muscle cells). The DGC is responsible for anchoring the cytoskeleton to the extracellular matrix, which helps to maintain the structural integrity of muscle fibers. DAPs include several proteins that are involved in muscle contraction, such as syntrophin and dystrobrevin, as well as proteins that are involved in signaling pathways, such as caveolin-3 and utrophin. Mutations in genes encoding DAPs can also lead to muscle disorders, such as limb-girdle muscular dystrophy (LGMD) and myotonic dystrophy (DM). In summary, DAPs are a group of proteins that interact with dystrophin and are essential for maintaining the structural integrity of muscle fibers. Mutations in genes encoding DAPs can lead to muscle disorders, highlighting the importance of these proteins in muscle health.

Dystroglycans are a group of proteins that play a crucial role in the structure and function of muscle cells and other tissues in the human body. They are composed of two subunits, dystroglycan and alpha-dystroglycan, which are linked together by a disulfide bond. Dystroglycans are primarily found in the extracellular matrix of cells, where they interact with other proteins and molecules to provide structural support and stability to the cell. They also play a role in the transmission of mechanical forces across the cell membrane, helping to maintain the integrity of the cell and protect it from damage. In addition to their role in muscle cells, dystroglycans are also found in other tissues, including the brain, heart, and nervous system. Mutations in the genes that encode dystroglycan can lead to a number of genetic disorders, including muscular dystrophy, congenital muscular dystrophy, and congenital myasthenia gravis. These disorders are characterized by muscle weakness, wasting, and other symptoms that can be severe and life-threatening.

Sarcoglycans are a group of proteins that are involved in muscle function and are found in the sarcolemma, which is the plasma membrane of muscle cells. They are part of a larger group of proteins called dystrophin-associated glycoproteins (DAGs) that play a critical role in maintaining the structural integrity of muscle fibers. Sarcoglycans are important for maintaining the stability of the muscle sarcolemma, which helps to prevent the loss of calcium ions from the muscle cell and maintain proper muscle function. Mutations in the genes that encode for sarcoglycans can lead to a group of inherited muscle disorders known as sarcoglycanopathies, which are characterized by muscle weakness, wasting, and degeneration. These disorders can range in severity from mild to life-threatening and can affect both skeletal and cardiac muscles.

Cytoskeletal proteins are a diverse group of proteins that make up the internal framework of cells. They provide structural support and help maintain the shape of cells. The cytoskeleton is composed of three main types of proteins: microfilaments, intermediate filaments, and microtubules. Microfilaments are the thinnest of the three types of cytoskeletal proteins and are composed of actin filaments. They are involved in cell movement, cell division, and muscle contraction. Intermediate filaments are thicker than microfilaments and are composed of various proteins, including keratins, vimentin, and desmin. They provide mechanical strength to cells and help maintain cell shape. Microtubules are the thickest of the three types of cytoskeletal proteins and are composed of tubulin subunits. They play a crucial role in cell division, intracellular transport, and the maintenance of cell shape. Cytoskeletal proteins are essential for many cellular processes and are involved in a wide range of diseases, including cancer, neurodegenerative disorders, and muscle diseases.

The Dystrophin-Associated Protein Complex (DAPC) is a group of proteins that interact with the protein dystrophin, which is encoded by the DMD gene. Dystrophin is a large, rod-shaped protein that is primarily found in muscle cells and helps to provide structural support to the muscle fibers. When dystrophin is absent or mutated, as occurs in Duchenne muscular dystrophy (DMD), the DAPC is disrupted, leading to muscle weakness and wasting. The DAPC is composed of several proteins, including sarcoglycans, dystroglycans, syntrophins, and dystrobrevins. These proteins help to anchor the dystrophin protein to the extracellular matrix and the cytoskeleton, forming a stable structure that provides mechanical support to the muscle fibers. In addition to its role in muscle function, the DAPC has been implicated in a variety of other cellular processes, including cell adhesion, migration, and signaling.

Morpholinos are a class of synthetic oligonucleotides that are used in various fields of medicine, including gene therapy and research. They are designed to bind to specific RNA sequences, either to inhibit their function or to modify their structure. In the context of gene therapy, morpholinos are used to target and silence specific genes that are involved in the development or progression of diseases. They can be delivered directly to cells or tissues using various delivery methods, such as viral vectors or nanoparticles. In research, morpholinos are commonly used as tools to study gene function and regulation. They can be used to knock down or inhibit the expression of specific genes, allowing researchers to study the effects of gene silencing on cellular processes and pathways. Overall, morpholinos have shown promise as a versatile and effective tool for both therapeutic and research applications in the medical field.

Muscle proteins are proteins that are found in muscle tissue. They are responsible for the structure, function, and repair of muscle fibers. There are two main types of muscle proteins: contractile proteins and regulatory proteins. Contractile proteins are responsible for the contraction of muscle fibers. The most important contractile protein is actin, which is found in the cytoplasm of muscle fibers. Actin interacts with another protein called myosin, which is found in the sarcomeres (the functional units of muscle fibers). When myosin binds to actin, it causes the muscle fiber to contract. Regulatory proteins are responsible for controlling the contraction of muscle fibers. They include troponin and tropomyosin, which regulate the interaction between actin and myosin. Calcium ions also play a role in regulating muscle contraction by binding to troponin and causing it to change shape, allowing myosin to bind to actin. Muscle proteins are important for maintaining muscle strength and function. They are also involved in muscle growth and repair, and can be affected by various medical conditions and diseases, such as muscular dystrophy, sarcopenia, and cancer.

Oligoribonucleotides, antisense are short RNA molecules that are designed to bind to specific messenger RNA (mRNA) molecules and prevent them from being translated into protein. These molecules are often used as a form of gene therapy to treat genetic disorders caused by the overexpression or underexpression of specific genes. Antisense oligonucleotides work by binding to the complementary sequence of the target mRNA, which causes the mRNA to be degraded or prevented from being translated into protein. This can help to regulate the expression of specific genes and potentially treat a variety of diseases.

Spectrin is a protein that is found in the cytoskeleton of cells, particularly in red blood cells. It is a key component of the membrane skeleton, which helps to maintain the shape and stability of the cell membrane. Spectrin is also involved in the transport of other proteins and molecules within the cell, and plays a role in the regulation of cell signaling pathways. In the medical field, spectrin is often studied in relation to diseases such as sickle cell anemia, which is caused by mutations in the spectrin gene.

Caveolin 3 is a protein that is primarily expressed in skeletal muscle cells. It is a component of caveolae, which are small, flask-shaped invaginations of the plasma membrane that are involved in various cellular processes, including signal transduction, cholesterol homeostasis, and endocytosis. In the medical field, caveolin 3 is often studied in the context of muscle diseases, particularly those that affect skeletal muscle. Mutations in the caveolin 3 gene have been associated with a number of muscle disorders, including limb-girdle muscular dystrophy type 2A (LGMD2A), which is a progressive muscle wasting disorder that primarily affects the muscles of the shoulders and hips. Caveolin 3 is also involved in the development and function of muscle fibers, and changes in its expression or function have been linked to various other muscle disorders, as well as to cancer and other diseases.

Membrane proteins are proteins that are embedded within the lipid bilayer of a cell membrane. They play a crucial role in regulating the movement of substances across the membrane, as well as in cell signaling and communication. There are several types of membrane proteins, including integral membrane proteins, which span the entire membrane, and peripheral membrane proteins, which are only in contact with one or both sides of the membrane. Membrane proteins can be classified based on their function, such as transporters, receptors, channels, and enzymes. They are important for many physiological processes, including nutrient uptake, waste elimination, and cell growth and division.

Actinin is a family of proteins that are primarily found in the cytoskeleton of muscle cells. They are involved in maintaining the structural integrity of muscle fibers and play a role in muscle contraction and relaxation. Actinin is also found in non-muscle cells, where it has been implicated in a variety of cellular processes, including cell adhesion, migration, and differentiation. In the medical field, actinin is often studied in the context of muscle diseases, such as muscular dystrophy, and as a potential target for the development of new treatments for these conditions.

Dilated cardiomyopathy is a medical condition characterized by the enlargement and weakening of the heart muscle, specifically the ventricles, which are the lower chambers of the heart responsible for pumping blood out to the rest of the body. This enlargement causes the heart to become weakened and unable to pump blood efficiently, leading to symptoms such as shortness of breath, fatigue, and swelling in the legs and ankles. Dilated cardiomyopathy can be caused by a variety of factors, including genetics, infections, alcohol and drug abuse, and certain medications. It can also be a complication of other heart conditions, such as hypertension or coronary artery disease. Diagnosis of dilated cardiomyopathy typically involves a physical examination, electrocardiogram (ECG), echocardiogram, and other imaging tests. Treatment may include medications to improve heart function, lifestyle changes such as a heart-healthy diet and exercise, and in some cases, surgery or heart transplantation.

Oligonucleotides, antisense are short, synthetic DNA or RNA molecules that are designed to bind to specific messenger RNA (mRNA) molecules and prevent them from being translated into proteins. This process is called antisense inhibition and can be used to regulate gene expression in cells. Antisense oligonucleotides are typically designed to target specific sequences within a gene's mRNA, and they work by binding to complementary sequences on the mRNA molecule, causing it to be degraded or prevented from being translated into protein. This can be used to either silence or activate specific genes, depending on the desired effect. Antisense oligonucleotides have been used in a variety of medical applications, including the treatment of genetic disorders, cancer, and viral infections. They are also being studied as potential therapeutic agents for a wide range of other diseases and conditions.

The mdx mouse contains a nonsense mutation in exon 23, leading to a shortened dystrophin protein. Levels of dystrophin in this ... Dystrophin supports muscle fiber strength, and the absence of dystrophin reduces muscle stiffness, increases sarcolemmal ... Blake DJ, Weir A, Newey SE, Davies KE (April 2002). "Function and genetics of dystrophin and dystrophin-related proteins in ... Blake DJ, Weir A, Newey SE, Davies KE (April 2002). "Function and genetics of dystrophin and dystrophin-related proteins in ...
A dystrophin-associated protein is a protein that helps to form the connection between intracellular dystrophin and the ... Dystrophin-Associated Proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH) v t e (Articles with ...
The dystrophin-associated protein complex includes dystrophin. Dystrophin binds to actin of the cytoskeleton, and also to ... The dystrophin-associated protein complex, also known as the dystrophin-associated glycoprotein complex is a multiprotein ... The dystrophin-associated protein complex also contains dystrophin-associated proteins. This includes a four subunit ... In the epithelia of the kidney, dystrophin may be replaced with utrophin. Aquaporin 4 may be connected to the dystrophin- ...
Stoeckert C (1997-03-16). "Dystrophin". Catalogue of Regulatory Elements. University of Pennsylvania. Archived from the ...
These include; dystrophin, a multidomain cytoskeletal protein; utrophin, a dystrophin-like protein; vertebrate YAP protein, ... Bork P, Sudol M (December 1994). "The WW domain: a signalling site in dystrophin?". Trends in Biochemical Sciences. 19 (12): ... a new amino acid motif present in single or multiple copies in various proteins including dystrophin and the SH3-binding Yes- ...
... including dystrophin, which is a key component of the DGC that interacts with sarcospan. The loss of dystrophin results in ... Dystrophin is required for proper localization of SSPN. SSPN is also an essential regulator of Akt signaling pathways. Without ... SSPN regulates the amount of Utrophin produced by the UGC to restore laminin binding due to the absence of dystrophin. If ... It is part of the dystrophin-associated glycoprotein complex (DGC), which is a protein complex found in muscle cells that helps ...
Roberts RG, Bobrow M, Bentley DR (March 1992). "Point mutations in the dystrophin gene". Proceedings of the National Academy of ... January 2004). "DGGE-based whole-gene mutation scanning of the dystrophin gene in Duchenne and Becker muscular dystrophy ...
Radojevic V, Lin S, Burgunder JM (2000). "Differential expression of dystrophin, utrophin, and dystrophin-associated proteins ... The dystrophin-glycoprotein complex (DGC) is a multisubunit protein complex that spans the sarcolemma and provides structural ... There are 3 main subcomplexes of the DGC: the cytoplasmic proteins dystrophin (DMD; MIM 300377) and syntrophin (SNTA1; MIM ... "Entrez Gene: SGCB sarcoglycan, beta (43kDa dystrophin-associated glycoprotein)". Yoshida M, Ozawa E (1991). "Glycoprotein ...
"Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix". Nature. 355 (6362): ... Dystrophin binds to intracellular actin cables. In this way, the dystroglycan complex, which links the extracellular matrix to ... Rentschler S, Linn H, Deininger K, Bedford MT, Espanel X, Sudol M (April 1999). "The WW domain of dystrophin requires EF-hands ... Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in Homo sapiens on ...
The lack of dystrophin that causes Duchenne muscular dystrophy results in secondary loss of other dystrophin-complex components ... The second resulted in the separate dystrophin and utrophin genes. In addition, sequence alignments of dystrophin family ... The dystrobrevin loss resulted from a weakening of dystrophin's interaction with the membrane-bound dystrophin-glycoprotein ... "Dystrobrevin increases dystrophin's binding to the dystrophin-glycoprotein complex and provides protection during cardiac ...
Moiseeva EP, Belkin AM, Spurr NK, Koteliansky VE, Critchley DR (Jul 1996). "A novel dystrophin/utrophin-associated protein is ... Belkin AM, Burridge K (1995). "Association of aciculin with dystrophin and utrophin". J. Biol. Chem. 270 (11): 6328-37. doi: ... 2000). "Aciculin and its relation to dystrophin: immunocytochemical studies in human normal and Duchenne dystrophy quadriceps ... a component of the dystrophin/utrophin cytoskeleton predominantly expressed in smooth muscle". Eur. J. Biochem. 248 (3): 634-43 ...
Because dystrophin is located on the X chromosome, dystrophinopathy mainly affects males, whereas females range from being ... Dystrophin abnormalities in X-linked dilated cardiomyopathy". Circulation. 95 (10): 2344-7. doi:10.1161/01.cir.95.10.2344. PMID ... Dystrophinopathy refers to a spectrum of diseases due to mutations in the DMD gene, which encodes for the dystrophin protein ...
This protein is a component of the dystrophin-associated protein complex (DPC). The DPC consists of dystrophin and several ... Blake DJ, Nawrotzki R, Loh NY, Górecki DC, Davies KE (1998). "β-dystrobrevin, a member of the dystrophin-related protein family ... Blake DJ, Hawkes R, Benson MA, Beesley PW (1999). "Different Dystrophin-like Complexes Are Expressed in Neurons and Glia". J. ... Ahn AH, Kunkel LM (1995). "Syntrophin binds to an alternatively spliced exon of dystrophin". J. Cell Biol. 128 (3): 363-71. doi ...
Blake DJ, Nawrotzki R, Loh NY, Górecki DC, Davies KE (January 1998). "beta-dystrobrevin, a member of the dystrophin-related ... This gene encodes dystrobrevin beta, a component of the dystrophin-associated protein complex (DPC). The DPC consists of ... "Entrez Gene: DTNB dystrobrevin, beta". Blake DJ, Hawkes R, Benson MA, Beesley PW (1999). "Different dystrophin-like complexes ... Dystrobrevin beta is thought to interact with syntrophin and the DP71 short form of dystrophin. Alternatively spliced ...
Researchers incorporated the 2.4 Mb dystrophin gene, in which a mutation is a key causal element of Duchenne muscular dystrophy ... Previous attempts at correctly expressing dystrophin have failed. Due to its large size, it has never before been successfully ... The resulting HAC was mitotically stable, and correctly expressed dystrophin in chimeric mice. ... containing the 2.4 Mb entire human dystrophin gene". Molecular Therapy. 17 (2): 309-17. doi:10.1038/mt.2008.253. PMC 2835068. ...
Bork P, Sudol M (December 1994). "The WW domain: a signalling site in dystrophin?". Trends in Biochemical Sciences. 19 (12): ... a new amino acid motif present in single or multiple copies in various proteins including dystrophin and the SH3-binding Yes- ...
Dystrophin is a large, rod-like cytoskeletal protein found at the inner surface of muscle fibers. Dystrophin is missing in ... The protein encoded by this gene is a peripheral membrane protein found associated with dystrophin and dystrophin-related ... Blake DJ, Hawkes R, Benson MA, Beesley PW (1999). "Different dystrophin-like complexes are expressed in neurons and glia". J. ... Ahn AH, Kunkel LM (1995). "Syntrophin binds to an alternatively spliced exon of dystrophin". J. Cell Biol. 128 (3): 363-71. doi ...
McClorey G, Fall AM, Moulton HM, Iversen PL, Rasko JE, Ryan M, Fletcher S, Wilton SD (October 2006). "Induced dystrophin exon ... Fletcher S, Honeyman K, Fall AM, Harding PL, Johnsen RD, Wilton SD (February 2006). "Dystrophin expression in the mdx mouse ...
Where dystrophin is present, the tests indicate the amount and molecular size of dystrophin, helping to distinguish DMD from ... It is caused by a mutation in the gene for the protein dystrophin. Dystrophin is important to maintain the muscle fiber's cell ... This functional, yet truncated, form of dystrophin gave rise to the notion that shorter dystrophin can still be therapeutically ... which are believed to be the result of inadequate dystrophin in the brain. DMD is caused by a mutation of the dystrophin gene, ...
Epsilon sarcoglycan itself is part of the dystrophin-associated protein (DAP) complex that binds the sarcolemma of muscle cells ... Ervasti, James M. (2013-01-01). "Structure and Function of the Dystrophin-Glycoprotein Complex". Madame Curie Bioscience ...
The dystrophin-glycoprotein complex (DGC) comprises a group of proteins that are critical to the stability of muscle fiber ... Components of the DGC include dystrophin (MIM 300377), which is deficient in Duchenne muscular dystrophy (DMD; MIM 310200); ... "Entrez Gene: SGCA sarcoglycan, alpha (50kDa dystrophin-associated glycoprotein)". Bowe MA, Mendis DB, Fallon JR (Feb 2000). " ... and dystrophin molecules in normal skeletal myofiber: triple immunogold labeling electron microscopy". Microscopy Research and ...
1996). "Characterization of DRP2, a novel human dystrophin homologue". Nat. Genet. 13 (2): 223-6. doi:10.1038/ng0696-223. PMID ...
Dystrophin is an integral part of the muscular structure, an absence of dystrophin can cause impairments such as: healthy ... The muscle protein, dystrophin, is in most muscle cells and works to strengthen the muscle fibers and protect them from injury ... Gao, Quan Q.; McNally, Elizabeth M. (2015-06-24). "The Dystrophin Complex: Structure, Function, and Implications for Therapy". ...
Badorff C; Lee G. H.; Knowlton K. U. (2000). "Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex". ...
... both in those muscle fibers lacking dystrophin and in rare, revertant fibers that express dystrophin. No reports have yet ... "Role of dystrophin and utrophin for assembly and function of the dystrophin glycoprotein complex in non-muscle tissue" (PDF). ... 1997). "Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy". Cell. 90 (4): 717-27. doi:10.1016/S0092 ... The name is a short form for ubiquitous dystrophin. The protein encoded by this gene is a component of the cytoskeleton. ...
Radojevic V, Lin S, Burgunder JM (2000). "Differential expression of dystrophin, utrophin, and dystrophin-associated proteins ... "Entrez Gene: SGCD sarcoglycan, delta (35kDa dystrophin-associated glycoprotein)". Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS ... which is a subcomplex of the dystrophin-glycoprotein complex (DGC). DGC forms a link between the F-actin cytoskeleton and the ...
The disease-causing mutations in the α to δ genes cause disruptions within the dystrophin-associated protein (DAP) complex in ... Gamma-sarcoglycan is one of several sarcolemmal transmembrane glycoproteins that interact with dystrophin, probably to provide ... "Entrez Gene: SGCG sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein)". Noguchi S, McNally EM, Ben Othmane K, ... "Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy". Science. 270 (5237): 819 ...
Gong TW, Besirli CG, Lomax MI (2002). "MACF1 gene structure: a hybrid of plectin and dystrophin". Mamm. Genome. 12 (11): 852-61 ... a hybrid of dystonin and dystrophin that can interact with the actin and microtubule cytoskeletons". J. Cell Biol. 147 (6): ... a human homologue of Drosophila kakapo with a close structural similarity to plectin and dystrophin". Biochem Biophys Res ...
Enteroviral protease 2A can cleave the cytoskeletal dystrophin protein in cardiomyocytes disrupting the dystrophin glycoprotein ... Additionally, dystrophin deficiency has been shown to increase the severity in dilated cardiomyopathy in a mouse model for DMD ... The cleavage site of dystrophin by protease 2A occurs in the hinge 3 region of the protein resulting a disruption of DCG ... Xiong, D; Lee, G.-H.; Badorff, C.; Dorner, A.; Lee, S.; Wolf, P.; Knowlton, K. U. (2002). "Dystrophin deficiency markedly ...
Mutations in dystrophin and Laminin, alpha 2 (LAMA2) have also been implicated in this disease. Esthesioneuroblastoma is of ... December 2018). "Genomic analysis identifies frequent deletions of Dystrophin in olfactory neuroblastoma". Nature ...
In contrast, AK animals showed similar dystrophin levels as controls. Conclusion: Dystrophin is ubiquitously expressed by ... it is hypothesized that dystrophin plays a role in neuronal excitability. Here, we aimed to study brain dystrophin distribution ... it is hypothesized that dystrophin plays a role in neuronal excitability. Here, we aimed to study brain dystrophin distribution ... nor in the regional dystrophin distribution between AK and control animals. Quantitatively, hippocampal full-length dystrophin ...
An absence of dystrophin in muscle has a massive impact throughout muscle development, and Duchene Muscular Dystrophy (DMD) is ... The disruption of the dystrophin-glycoprotein complex (DGC) is caused by a mutation in the dmd gene, which effects muscle ... Yazid, Muhammad DaIn Bin (2017). Analysis of cell signalling in dystrophin-deficient myoblasts. University of Birmingham. Ph.D ... In this study, dfd13 (dystrophin-deficient) and C2C12 (non-dystrophic) myoblasts were cultured in low mitogen conditions for 10 ...
For sarcolemmal stability, dystrophin and the dystrophin-associated glycoproteins (DAGs) are important elements. [3, 4] ... High-level dystrophin expression after adenovirus-mediated dystrophin minigene transfer to skeletal muscle of dystrophic dogs: ... The dystrophin gene is located on the short arm of chromosome X near the p21 locus and codes for the large protein Dp427, which ... Genetic defects and dystrophin. In the X-linked forms of MD, such as the Duchenne and Becker dystrophies, the defect is located ...
Functionality of the resulting truncated dystrophin proteins was investigated in muscle of adult dystrophin-deficient mdx mice ... One of the major challenges of this method is the large size of the dystrophin cDNA of ~14 kb, exceeding the packaging capacity ... Two novel mini-dystrophins retained the centrally-located nNOS-anchoring domain in order to achieve sarcolemmal nNOS ... Optimisation of internally deleted dystrophin constructs. Authors. Dr. Mojgan Reza, Dr. Steven Hector Laval, Miss Stephanie Jan ...
We undertook the clinical feature examination and dystrophin analysis using multiplex ... Mutation spectrum of dystrophin gene in malaysian patients with Duchenne/Becker muscular dystrophy; Rani AQ, Sasongko TH, ... Two novel mutations have been detected in the Dystrophin gene and our results were compatible with other studies where the ... Mutation spectrum of dystrophin gene in malaysian patients with Duchenne/Becker muscular dystrophy. ...
DMD: dystrophin. *DMPK: DM1 protein kinase. *DNAH5: dynein axonemal heavy chain 5 ...
... provides instructions for making a protein called dystrophin. Learn about this gene and related health conditions. ... Dystrophin: more than just the sum of its parts. Biochim Biophys Acta. 2010 Sep;1804(9):1713-22. doi: 10.1016/j.bbapap.2010.05. ... The dystrophin complex acts as an anchor, connecting each muscle cells structural framework (cytoskeleton) with the lattice of ... Ehmsen J, Poon E, Davies K. The dystrophin-associated protein complex. J Cell Sci. 2002 Jul 15;115(Pt 14):2801-3. doi: 10.1242/ ...
... which is made up of proteins called dystrophins and dystroglycans. The large dystrophin complex strengthens muscle fibers and ... SGCA gene mutations may prevent the sarcoglycan complex from forming or from binding to and stabilizing the dystrophin complex ... It helps maintain the structure of muscle tissue by attaching (binding) to and stabilizing the dystrophin complex, ...
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 ...
Kilimann, M. W., Pizzuti, A., Grompe, M., & Caskey, C. T. (1992). Point mutations and polymorphisms in the human dystrophin ... Kilimann, MW, Pizzuti, A, Grompe, M & Caskey, CT 1992, Point mutations and polymorphisms in the human dystrophin gene ... Point mutations and polymorphisms in the human dystrophin gene identified in genomic DNA sequences amplified by multiplex PCR. ... Presumably, in these cases, the deficiency is caused by minor structural lesions of the dystrophin gene. However, to date, only ...
... it modulates cardiac differentiation and proliferation by interacting with the dystrophin-glycoprotein complex, Yap and ERK- ... derived from mouse and human induced pluripotent stem cells through a mechanism that involves the disassembly of the dystrophin ... Constantin, B. Dystrophin complex functions as a scaffold for signalling proteins. Biochim. Biophys. Acta 1838, 635-642 (2013) ... Campbell, K. P. & Kahl, S. D. Association of dystrophin and an integral membrane glycoprotein. Nature 338, 259-262 (1989) ...
... the dystrophin is nearly absent, whereas in BMD the dystrophin is present but reduced in size or amount (1). ... Abnormal dystrophin has also been identified as a potential susceptibility gene for viral infection and as factor that markedly ... The dystrophin gene The dystophin protein provides a structural link between myocyte cytoskeleton and extracellular matrix ... recessive disorders characterised by an abnormality in the dystrophin gene and in which elevated serum creatinine kinase ...
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Often referred to as a molecular "shock absorber," dystrophin stabilizes the sarcolemma during muscle contractions to prevent ... DMD causes progressive muscle wasting stemming from the root genetic cause of missing dystrophin in muscle cells. ... was designed to deliver a trimmed down form of dystrophin to compensate for the deficit. ...
Dystrophin-glycoprotein complex bridges the inner cytoskeleton (F-actin) and the basal lamina. Mutations in all sarcoglycans, ... Dystrophin-glycoprotein complex bridges the inner cytoskeleton (F-actin) and the basal lamina. Mutations in all sarcoglycans, ...
While DMD mutations cause virtually no functional dystrophin to be made, people with BMD make dystrophin that is partially ... The dystrophin protein keeps the muscle cell membrane from breaking or tearing when our muscles contract and relax. Because it ... BMD occurs when the dystrophin protein thats made from a particular gene on the X chromosome is only partially functional. ... In addition to its force-transfer role, dystrophin provides the scaffold for holding numerous molecules in place near the cell ...
The absence of the dystrophin protein is due to a defective gene commonly found in males. Dystrophin helps muscle cells ...
When dystrophin is missing in the body, muscle cells are easily damaged, which causes progressive muscle weakness in the entire ... It is caused by a mutation in the gene that encodes for dystrophin, a lubricating protein supports muscle fiber strength. ...
The gene for dystrophin is an example of alternative splicing: full-length dystrophin is the major isoform expressed in muscle ...
Absence of dystrophin disrupts skeletal muscle signaling: roles of Ca2+, reactive oxygen species, and nitric oxide in the ...
... two novel dystrophin-binding proteins localized in neuronal cells." in: The Journal of biological chemistry, Vol. 275, Issue 21 ... that bind to components of mechanosenstive sodium channels and the extreme carboxy-terminal domain of dystrophin and dystrophin ...
The same repeats are also present in alpha-actinin, dystrophin and utrophin. Sequence alignments and phylogenetic trees of ... and dystrophin. The spectrin repeat forms a three-helix bundle. The second helix is interrupted by proline in some sequences. ...
It is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. DMD primarily affects males with ...
X-linked recessive disorder caused by mutation of DMD gene coding for dystrophin protein; boys present with calf hypertrophy, ... DMD-associated cardiomyopathy: Weakening & enlargement of the heart as a result of a lack of dystrophin in the myocardium; ...
... is characterized by progressive muscle degeneration and weakness due to the alterations of the dystrophin protein that keeps ... challenging because researchers do not understand completely the pathological consequences resulting from loss of dystrophin. ...
... and Dutch drugmaker Prosensas RNA-based therapeutic PRO051 restored dystrophin expression in patients with Duchenne Muscular ... Leiden University Medical Center (LUMC) and Dutch drugmaker Prosensas RNA-based therapeutic PRO051 restored dystrophin ...
Convergent regulation of skeletal muscle Ca2+ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase ... Convergent regulation of skeletal muscle Ca2+ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase ...
  • In addition to weakness of the skeletal muscles, serious cardiac problems can occur in both diseases, which can be caused by a wide variety of mutations in the dystrophin gene. (mda.org)
  • and to correlate it with specific dystrophin gene mutations. (mda.org)
  • Two novel mutations have been detected in the Dystrophin gene and our results were compatible with other studies where the majority of the mutations (62.8%) are located in the distal hotspot. (afpm.org.my)
  • Mutations that cause Becker muscular dystrophy, which typically has milder features and appears at a later age than Duchenne muscular dystrophy, usually lead to an abnormal version of dystrophin that retains some function. (medlineplus.gov)
  • Mutations that cause the more severe Duchenne muscular dystrophy typically prevent any functional dystrophin from being produced. (medlineplus.gov)
  • The mutations that cause X-linked dilated cardiomyopathy preferentially affect the activity of dystrophin in cardiac muscle cells. (medlineplus.gov)
  • As a result of these mutations, affected individuals typically have little or no functional dystrophin in the heart. (medlineplus.gov)
  • The mutations that cause X-linked dilated cardiomyopathy often lead to reduced amounts of dystrophin in skeletal muscle cells. (medlineplus.gov)
  • SGCA gene mutations may prevent the sarcoglycan complex from forming or from binding to and stabilizing the dystrophin complex. (medlineplus.gov)
  • Both point mutations are frameshift mutations in exons 12 and 48, respectively, and are closely followed by stop codons, thus explaining the functional deficiency of the dystrophin gene products in both patients. (elsevierpure.com)
  • Among them, dystrophin strengthens the sarcolemma through protein-lipid interactions, and its absence due to gene mutations leads to the severe Duchenne muscular dystrophy. (cea.fr)
  • Milder course in Duchenne patients with nonsense mutations and no muscle dystrophin. (bvsalud.org)
  • Diagnosis of Mutations in the dystrophin gene can cause Duchenne these disorders is based on clinical presentation, muscular dystrophy or Becker muscular dystrophy. (who.int)
  • 90% of cases, mutations that from mutation in the dystrophin gene (located on short disrupt the reading frame (frame shift) lead to arm of X chromosome, Xp21). (who.int)
  • They are caused by mutations of the dystrophin gene, the largest known human gene, at the Xp21.2 locus. (msdmanuals.com)
  • In Becker dystrophy, the mutations result in production of abnormal dystrophin or insufficient dystrophin. (msdmanuals.com)
  • Deletions, not duplications or small mutations, are the predominante new mutations in the dystrophin gene. (cdc.gov)
  • Hippocampal full-length dystrophin (Dp427) levels are upregulated in human TLE, but not in AK rats, possibly indicating a compensatory mechanism in the chronic epileptic human brain. (frontiersin.org)
  • Dystrophin accounts for only approximately 0.002% of the proteins in striated muscle, but it has obvious importance in the maintenance of the muscle's membrane integrity. (medscape.com)
  • In skeletal and cardiac muscles, dystrophin is part of a group of proteins (a protein complex) that work together to strengthen muscle fibers and protect them from injury as muscles contract and relax. (medlineplus.gov)
  • The dystrophin complex acts as an anchor, connecting each muscle cell's structural framework (cytoskeleton) with the lattice of proteins and other molecules outside the cell (extracellular matrix). (medlineplus.gov)
  • The dystrophin complex may also play a role in cell signaling by interacting with proteins that send and receive chemical signals. (medlineplus.gov)
  • It helps maintain the structure of muscle tissue by attaching (binding) to and stabilizing the dystrophin complex, which is made up of proteins called dystrophins and dystroglycans. (medlineplus.gov)
  • A macromolecular complex of proteins that includes DYSTROPHIN and DYSTROPHIN-ASSOCIATED PROTEINS. (bvsalud.org)
  • Studying the role of dystrophin-associated proteins in influencing Becker muscular dystrophy disease severity. (cdc.gov)
  • The investigators hope to recruit 800 participants who have a diagnosis of DMD or BMD with a documented mutation of the dystrophin gene, and who can cooperate with Doppler echocardiogram testing and skeletal-muscle testing. (mda.org)
  • The disruption of the dystrophin-glycoprotein complex (DGC) is caused by a mutation in the dmd gene, which effects muscle integrity, resulting in progressive muscle degeneration and weakness. (bham.ac.uk)
  • To conclude, destabilisation of the plasma membrane owing to a dystrophin mutation causes cell signalling alterations which minidystrophin restoration can partly improve. (bham.ac.uk)
  • It is caused by a mutation in the gene that encodes for dystrophin, a lubricating protein supports muscle fiber strength. (guidestar.org)
  • Analysis of dystrophin gene in Iranian Duchenne and Becker muscular dystrophies patients and identification of a novel mutation. (cdc.gov)
  • Duchenne and Becker muscular dystrophies are inherited X-linked, recessive disorders characterised by an abnormality in the dystrophin gene and in which elevated serum creatinine kinase activity is observed. (escardio.org)
  • The brother that got the red X, fertilized egg number 4, ends up getting DMD because he has no working dystrophin genes. (thetech.org)
  • the tadpoles showed reduced expression of cα(E)-catenin , small muscle protein, dystrophin , and myosin light chain genes. (biomedcentral.com)
  • One promising approach uses an injection of small, harmless viruses to deliver therapeutic dystrophin-producing genes directly into cells in the muscle. (medlineplus.gov)
  • NIH-supported researchers have been studying ways to deliver dystrophin genes to affected muscles with fewer side effects. (medlineplus.gov)
  • Dystrophin is part of a protein complex that connects the cytoskeleton to the extracellular matrix. (frontiersin.org)
  • Dystrophin aggregates as a homotetramer at the costomeres in skeletal muscles, as well as associates with actin at its N-terminus and the DAG complex at the C-terminus, forming a stable complex that interacts with laminin in the extracellular matrix. (medscape.com)
  • Abnormal dystrophin has also been identified as a potential susceptibility gene for viral infection and as factor that markedly increases enterovirus induced cardiomyopathy (2). (escardio.org)
  • The absence of dystrophin leads to myofiber membrane fragility that results in the progressive muscular degeneration that characterizes DMD ( Sussman, 2002 ). (frontiersin.org)
  • An absence of the muscle protein dystrophin is the underlying cause of Duchenne muscular dystrophy (DMD) , while a partial lack of dystrophin is the cause of Becker muscular dystrophy (BMD) . (mda.org)
  • An absence of dystrophin in muscle has a massive impact throughout muscle development, and Duchene Muscular Dystrophy (DMD) is one of the consequences. (bham.ac.uk)
  • We are pleased to share the good news that several regulatory authorities have approved the re-start of our Phase 3 ambulatory trial (CIFFREO) for our investigational mini-dystrophin gene therapy for Duchenne muscular dystrophy. (parentprojectmd.org)
  • We undertook the clinical feature examination and dystrophin analysis using multiplex ligation-dependent probe amplification (MLPA) and direct DNA sequencing of selected exons in a cohort of 35 Malaysian Duchenne/Becker muscular dystrophy (DMD/BMD) patients. (afpm.org.my)
  • About one third of Duchenne muscular dystrophy (DMD) patients have no gross DNA rearrangements in the dystrophin gene detectable by Southern blot analysis or multiplex exon amplification. (elsevierpure.com)
  • Both Duchenne (DMD) and Becker (BMD) muscular dystrophies are X-linked, recessive disorders in which the genetic locus has been identified as an abnormality in the dystrophin gene. (escardio.org)
  • Considered one of the most severe forms of muscular dystrophy, DMD causes progressive muscle wasting stemming from the root genetic cause of missing dystrophin in muscle cells. (medscape.com)
  • Duchenne muscular dystrophin deficiency and cause DMD. (who.int)
  • Functionally, dystrophin expressed in the CNS plays an important role in the clustering of neurotransmitter receptors and water- and ion channels to the cellular membrane. (frontiersin.org)
  • Campbell, K. P. & Kahl, S. D. Association of dystrophin and an integral membrane glycoprotein. (nature.com)
  • 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)
  • 5%) of dystrophin, a protein in the muscle cell membrane. (msdmanuals.com)
  • Advances in molecular biology techniques illuminate the genetic basis underlying all types of MD: defects in the genetic code for dystrophin, a 427-kd skeletal muscle protein (Dp427). (medscape.com)
  • Often referred to as a molecular "shock absorber," dystrophin stabilizes the sarcolemma during muscle contractions to prevent degeneration. (medscape.com)
  • The large dystrophin complex strengthens muscle fibers and protects them from injury as muscles tense (contract) and relax. (medlineplus.gov)
  • To screen for microheterogeneities in the dystrophin gene, we applied analysis by chemical mismatch cleavage to thirteen exons amplified in multiplex sets by the polymerase chain reaction. (elsevierpure.com)
  • Evaluation of multiplex ligation-dependent probe amplification analysis versus multiplex polymerase chain reaction assays in the detection of dystrophin gene rearrangements in an Iranian population subset. (cdc.gov)
  • The dystrophin gene is located on the short arm of chromosome X near the p21 locus and codes for the large protein Dp427, which contains 3685 amino acids. (medscape.com)
  • This matters in this case because the DNA differences that cause DMD are found in the dystrophin gene on the X chromosome. (thetech.org)
  • A fusion peptide directs enhanced systemic dystrophin exon skipping and functional restoration in dystrophin-deficient mdx mice. (ox.ac.uk)
  • When dystrophin is missing in the body, muscle cells are easily damaged, which causes progressive muscle weakness in the entire body. (guidestar.org)
  • Finally, minidystrophintransfection of both types of myoblasts was utilised to examine the effect, especially in dystrophin-deficient myoblasts. (bham.ac.uk)
  • Myoblasts can be visualized using desmin and dystrophin or desmin and vimentin. (cdc.gov)
  • Presumably, in these cases, the deficiency is caused by minor structural lesions of the dystrophin gene. (elsevierpure.com)
  • Pfizer has issued a community letter sharing that the FDA has lifted the clinical hold on the company's Phase 3 ambulatory trial (CIFFREO) for their investigational mini-dystrophin gene therapy product for Duchenne. (parentprojectmd.org)
  • SRP-9001, a single-dose recombinant gene therapy administered as an intravenous infusion, was designed to deliver a trimmed down form of dystrophin to compensate for the deficit. (medscape.com)
  • Therefore, understanding these structural changes may help in the design of rationalized shortened dystrophins for gene therapy. (cea.fr)
  • Skeletal and cardiac muscle cells without enough functional dystrophin become damaged as the muscles repeatedly contract and relax with use. (medlineplus.gov)
  • Complex genomic rearrangements in the dystrophin gene due to replication-based mechanisms. (cdc.gov)
  • In vitro , recombinant agrin promotes the division of cardiomyocytes that are derived from mouse and human induced pluripotent stem cells through a mechanism that involves the disassembly of the dystrophin-glycoprotein complex, and Yap- and ERK-mediated signalling. (nature.com)
  • Dystrophin can also be found in cardiac smooth muscles and in the brain (accounting for the slight mental retardation associated with this disease). (medscape.com)
  • Diagnosis is suggested clinically and is confirmed by genetic testing or analysis of the protein product (dystrophin) of the mutated gene. (msdmanuals.com)
  • Here, we aimed to study brain dystrophin distribution and expression in both, human and experimental temporal lobe epilepsy (TLE). (frontiersin.org)
  • Regional and cellular dystrophin distribution was evaluated in both human and rat hippocampi and in rat cerebellar tissue by immunofluorescent colocalization with neuronal (NeuN and calbindin) and glial (GFAP) markers. (frontiersin.org)
  • Dystrophin is ubiquitously expressed by astrocytes in the human and rat hippocampus and in the rat cerebellum. (frontiersin.org)
  • DMD , the largest known human gene, provides instructions for making a protein called dystrophin. (medlineplus.gov)
  • Dystrophin was expressed in all hippocampal pyramidal subfields and in the molecular-, Purkinje-, and granular cell layer of the cerebellum. (frontiersin.org)
  • In rat hippocampus and cerebellum there were neither differences in dystrophin positive cell types, nor in the regional dystrophin distribution between AK and control animals. (frontiersin.org)
  • In addition, hippocampal dystrophin levels were estimated by Western blot analysis in biopsies from TLE patients, post-mortem controls, amygdala kindled (AK)-, and control rats. (frontiersin.org)
  • This analysis covers approximately 20% of the dystrophin-coding sequence. (elsevierpure.com)
  • Less active forms of dystrophin may still function as a sarcolemmal anchor, but they may not be as effective a gateway regulator because they allow some leakage of intracellular substance. (medscape.com)
  • Two MDA-supported studies focusing on the dystrophin-deficient heart and its treatment are now under way at the five centers that comprise the MDA DMD Clinical Research Network. (mda.org)
  • Small amounts of dystrophin are present in nerve cells in the brain. (medlineplus.gov)
  • Since epilepsy is also supposed to constitute a comorbidity of DMD, it is hypothesized that dystrophin plays a role in neuronal excitability. (frontiersin.org)
  • In DMD, the dystrophin is nearly absent, whereas in BMD the dystrophin is present but reduced in size or amount (1). (escardio.org)
  • In contrast, AK animals showed similar dystrophin levels as controls. (frontiersin.org)