The contractile unit of a muscle cell is the sarcomere. Sarcomeres are mostly comprised of actin and myosin which pull and slide upon each other. These contractile units are linked end to end, like a chain, throughout the length of any given muscle. Certain proteins link the ends of these chains to the cell membrane. When a normally healthy individual exercises, some of these fibers, both in the sarcomere and at the connections to the cell wall, will be broken down due to damage (Leyva, 2013). Associated with this process includes the rebuilding of these fibers, in which the body builds back what was damaged stronger than before the damage occurred (Leyva, 2013). One of these end proteins is dystrophin. The purpose of this paper is to explore the implications of insufficient production of dystrophin, as in DMD.
Pathology
Duchenne Muscular Dystrophy (DMD) is an X-linked genetic disorder in which muscle cells do not reproduce dystrophin. This means that during the rebuilding of new muscle, the muscles of those individuals who have MD do not appropriately repair and rebuild the fibers containing dystrophin. In essence, it is similar to a minor tendon tear on a microscopic level happening on the inside of the muscle. Due to this dysfunctional rebuilding of these connective components, there is an even greater discrepancy between the amount of force the sarcomeres can produce and the amount of force the fibers which connect to the cell membrane can withstand. This causes more
2. The typical microscopic changes noted in the muscle tissue of someone with Duchenne’s muscular dystrophy is degenerating skeletal muscle cells. Surrounding these muscle cells is a large amount of endomysial connective tissue that is proliferating. A large number of macrophages can be seen whose responsibility is to eliminate cellular debris. Some muscle cells (fibers)
Muscle atrophy is the loss of skeletal muscle mass and function that occurs when there is a long period of inactivity of the muscles or defects in motor neuron's (Reilly, Beau 2015). Defects in the motor neurons that stimulate the muscle cause the muscle mass to decrease as proteins that initiate contractions of muscle dissipate. Stimulus is not transferred to the weakened muscle fibers effectively, reducing the contractile force possible for generation from the stimulus. Muscle mass increases upon recovery, as restimulation of the muscle enlarges fiber size, thus a greater contractile force can be generated from the stimulus.
Muscular dystrophy is a degenerating disease, in which the skeletal muscles degenerate, lose their strength, and cause increasing disability and deformity. Muscles attached to the bones through tendons are responsible for movement in the human body, however, in muscular dystrophy the muscles become progressively weak. As the muscle fibers
Duchenne muscular dystrophy was first discovered by Guillaume Benjamin Amand Duchenne in the 1860’s, but due to lack of medical knowledge little was known until the 1980’s. It was in 1986 that researchers that were supported by the MDA, muscular dystrophy association, identified the particular X-chromosome that leads to DMD, Duchenne muscular dystrophy. Dystrophin is the protein that is associated with the gene and was named in 1987.The DMD gene is the second largest gene to date, and it produces dystrophin.(Genome, 2013) Lack of the protein Dystrophin in the muscle cells causes them to weaken and become fragile. (MDA, 2015). DMD is an inherited disorder, but there are rare cases where it can spontaneously appear in a child with no previous family history due to a random mutation in moms X-chromosome. DMD is a gender specific disease that only appears in males.
Nowak KJ, & Davies KE. (2004). Duchenne muscular dystrophy and dystrophin: pathogenesis and opportunities for treatment. EMBO Reports, 5(9), 872-876. doi:10.1038/sj.embor.7400221
Duchenne Muscular Dystrophy (DMD) refers to the muscle appearing poorly nourished because of degeneration, which leads to muscle weakness and lost of muscle mass. DMD is a disorder that is caused by genetic mutations in the dystrophin gene. Dystrophin is a muscle that connects the cytoskeleton to the extracellular matrix (ECM). Tidy, D. C. (2016, April 15). When nonsense mutation or frameshift mutation occurs in dystrophin, it results in no protein at all, which causes a severe form of DMD. A dystrophin gene has more base pairs and more exons in comparison to most genes, which means the dysophin gene has a higher chance for mistakes during meiosis. The disorder affects one in 5000 newborn males. Tidy, D. C. (2016, April 15). Males have one
Muscular dystrophy (MD) is a rare, progressive disease relating to the weakening of skeletal muscles. There are more than 30 types of muscular dystrophy that are further divided into nine categories. Duchenne MD is the most common and acute form of this condition that accounts for 50% of all the cases. Duchenne MD (DMD) is most prevalent in males, between the ages of 3 and 5 (Norwood, FL, et al. 2009). This X-linked disease occurs for 1 in every 3,500 males, which results in confinement to a wheelchair (Blake et al., 2002). Becker MD (BMD) is a less severe type of this condition. A study conducted in the United Kingdom by Bushby, Thambyayah and Gardner-Medwin, the incidence of Becker MD was estimated to be 1 in 18,450 males at birth
Muscular dystrophy (MD) is a genetic disorder caused by incorrect or missing genetic information that leads to the gradual weakening of the muscle cells. Various causes lead to weak and deteriorating muscles depending on the type of muscular dystrophy the patient was affected by. However, there are many causes for muscular dystrophy due to the fact that there are thirty forms of muscular dystrophy, which are categorized under several categories. All are ultimately caused by autosomal recessive, autosomal dominant, sex-linked, and random mutations in very rare cases.
DMD is caused by a mutation in the X-linked dystrophin gene, which results in a dysfunctional dystrophin protein. Dystrophin is a cytoskeletal protein that provides mechanical stability to muscle cells by connecting the muscle sarcolemma to the basal lamina of the extracellular matrix (ECM), and without it there, the muscle cells typically undergo a process of degeneration and regeneration. This process is limited by the survival of satellite cells present since satellite cells can only undergo mitosis a limited amount of times. Sarcolemma instability typically results in excess intracellular amounts of both sodium and calcium, which causes ATP depletion and mitochondrial uncoupling (Horn & Schleip, 2012). Satellite cells only have a limited number times they can undergo mitosis, and once a patient can no longer generate healthy muscle cells, the patient will typically experience cell death. This cell death and necrosis usually
Muscular dystrophy is a combination of diseases passed down through genes identified by progressive degeneration of the skeletal or voluntary muscles.(Alicia Foose,PhD, Patricia Ardovino,PhD,2008, p.141). This occurs due to mixture of hypertrophy, atrophy, and necrosis muscle cells. The muscle fibers increase in muscle size and results in muscle weakness while the muscle undergoes necrosis, fat and connective tissue replace the muscle fibers.(Sheila Grossman, Carol Mattson Porth,p.461).There are nine types of muscular dystrophy according to Alicia Foose, and Patricia Ardovino“Duchenne, Becker, Emery-Dreifuss, Limb-girdle, facioscapulohumeral, myotonic, oculopharyngeal distal, and congenital.”Each disease
Muscles owe their ability to contract to structural units called sarcomeres, and a single muscle fiber can contain many thousands of these structures, aligned one next to the other. Each mature sarcomere is made up of precisely arranged and intertwined thin filaments of actin and thicker bundles of motor proteins, surrounded by other proteins. Sliding the motors along the filaments provides the force needed to contract the muscle. However, it was far from clear how sarcomeres, especially the arrays of thin-filaments, are assembled from scratch in developing muscles.
The Duchenne muscular dystrophy gene causes deletions of nucleotides which interrupts the translational reading frame. What could help restore the reading frame is by eliminating additional exons around the inherited deletion. The target exon for this restoration to happen is exon 51. Another treatment that could positively affect a patient with this disorder is using genome editing by creating a targeted frameshift. For this treatment to be effective nucleases are directed to sites within exons around the deleted region of the gene will insert a small indel that restores the translational reading frame (Hamm & Gersbach, 2016). Also, meganucleasese are used to insert small indels that will restore the reading frame of a modified Duchenne muscular dystrophy gene. This treatment is successful, majority of the time, however, if too many small indels are inserted into gene or not enough indels are inserted into the gene it could cause point mutation (Hamm & Gersbach, 2016). A point mutation could lead to missense mutation, nonsense mutation, neutral mutation, silent mutation, or frameshift mutation. The last treatment that could be used to help patients affected by this disorder is homologous recombination. This treatment does not have the same effect has the treatments above and it also downregulated in post-mitotic cells such as muscle fibers. Genome editing of the Duchenne muscular dystrophy gene has been successful in
The malfunctioning organelle is the microfilaments. First of all, the microfilaments are known for maintaining the shape of the cell and allowing organelles to move within the cell (Mader, 60). One can start by saying that when there is any failure in the microfilaments then the organelles of the cell will not properly move, shown in the “impaired intracellular movement of materials”, as stated in the laboratory results. Moreover, microfilaments are compared to the bones and muscles of the cell. Focusing on muscles, actin filaments’ role in the muscle cell is to strengthen it; therefore, any malfunction will lead to a weaker muscle, seeing the issue of “muscle weakness” in the patient’s history and even “muscle loss and deformity” in the physical
1. In terms of progressive weakness and degeneration of muscles one group of disorders is being connected from it and that disorder is called Muscular Dystrophy. It is said to be caused by mutations on the X chromosome and due to not being able to produce a protein called Dystrophin that plays a vital role in building and repairing muscles that cannot function properly. The said protein aids various elements within muscle cells together and bonds them all to the outer membrane or the sarcolemma. Without the presence of dystrophin, disruptions transpire in the sarcolemma results to weakening of muscles and may cause damage to the muscle cells.
Muscle Fibre Tear- When the muscles contract they create micro tears within the muscle and require protein in order to mend the muscles. These tears are repaired into stronger and denser fibres. For example if an individual went on the treadmill for 10 minutes, the hamstrings,