Faulty Gene Causes Myotonic Dystrophy

Researchers have found that in myotonic dystrophy (DM), the most common form of muscular dystrophy in adults, a faulty gene creates flawed mRNA that results in the loss of chloride channel protein (ClC-1) from the surface membrane of the main chloride channel in muscle, which causes degeneration and repetitive action potentials (myotonia). The findings were reported in the July 18, 2002, issue of Molecular Cell.

The investigators, from the University of Rochester Medical Center (New York, USA; www.rochester.edu), worked with a transgenic mouse model that mimics human DM. They found that faulty messenger RNA accumulates in the nuclei of cells in muscles from these animals. "Somehow the abnormal mRNA coming from the myotonic dystrophy gene builds up in the nucleus and prevents other RNAs from being spliced correctly. That is what causes this electrical misbehavior in patients with myotonic dystrophy,” said Dr. Charles Thornton, the neurologist who headed the research team.

The faulty mRNA inhibits the manufacture of the chloride channel protein (ClC-1), which is vital for maintaining the proper flow of electricity in muscles. Without the chloride channel, electrical signals in muscles stay "on” for too long, and muscle control becomes unstable.

Dr. Thornton said, "We believe this is the first example of an abnormal gene that has a harmful effect in the human body because the RNA that the gene produces is toxic. Bad RNA is the culprit and good RNA is the victim.”



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