Several forms of muscular dystrophy are attributed to mutations of single genes encoding several proteins of the dystrophin–glycoprotein complex. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are associated with mutations that affect dystrophin expression (Fig F11.2. 2); different forms of limb FIGURE F11.2.2 • Distribution of dystrophin in a patient girdle muscular dystrophy (LGMD) are caused by muta-with Duchenne muscular dystrophy (DMD). This crosstions in the genes found on the short arm of the X chromo-section of skeletal muscle was obtain from a patient diagnosed some encoding the four different sarcoglycans, and with DMD. Slide preparation similar to Fig F11.2.1. Compare another form of congenital muscular dystrophy (CMD) is the pattern and intensity of the dystrophin distribution within caused by a mutation in the gene encoding the 2 chain of affected muscle fibers to the normal individual. This muscle shows signs of hypertrophy. Some fibers do not have any muscle laminin. Recent research has successfully characexpression of dystrophin; others still express variable levels of terized the dystrophin gene and its products. Most cases dystrophin. 480. (Courtesy of Dr. Andrew G. Engel.) of DMD are caused by a high frequency of gene deletions that create frame shifts, resulting in the absence of dystrophin in affected muscle fibers. This finding in affected individuals opened the way to direct genetic testing and prenatal diagnosis.
Because of its inheritance as an X-linked recessive trait, DMD primarily affect boys (an estimated 1 in 3,500 boys worldwide). Onset of DMD is between 3 and 5 years of age and progresses rapidly. Most boys become unable to walk by age 12 and by age 20 must use a respirator to breathe. BMD is similar to DMD except that it progresses at a much slower rate. Symptoms usually appear at about age 12, and the ability to walk is lost at an average age of 25 to 30. At the current time, there is no known cure for muscular dystrophies, and available treatment is aimed at controlling symptoms to maximize quality of life. Intensive research efforts are directed to implement gene therapy
FIGURE F11.2.1 • Distribution of dystrophin in human into treatment of affected patients. One method may lead skeletal muscle. This cross section of skeletal muscle fibers from a healthy individual was immunostained with cells. To achieve that objective, specially engineered forms goat polyclonal antibody against dystrophin using of viruses need to be develop that would carry “normal” immunoperoxydase method. Since dystrophin and associated dystrophin-glycoprotein complexes connect the muscle genes, infect muscle cells, and induce cells to express dyscytoskeleton to the surrounding extracellular matrix through trophin. The other method that might be tried is transplanthe cell membrane, the localization of dystrophin outlines cell tation of “healthy” satellite (muscle stem) cells that can membrane. Note a regular shape of skeletal muscle cells and divide and differentiate into normal muscle cells. Stem cell pattern of dystrophin distribution. 480. (Courtesy of therapy has been tested in laboratory animals and yielded Dr. Andrew G. Engel.) encouraging results.
ATP is absent. This arrangement is known as the rigor configuration. The muscular stiffening and rigidity that begins at the moment of death is caused by lack of ATP and is known as rigor mortis. In an actively contracting muscle, this step ends with the binding of ATP to the myosin head.
Release is the second stage of the cycle; the myosin head is uncoupled from the thin filament.