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UA researchers find culprit behind skeletal muscle disease
Date:1/28/2014

A University of Arizona doctoral candidate has shown for the first time that genetic mutations in the titin gene can cause skeletal muscle myopathy, a disease in which muscle fibers do not function properly, resulting in muscle weakness. Myopathic disease can affect heart muscles as well as skeletal muscles, and titin is responsible for many problems associated with heart disease.

The research was done by Danielle Buck, a doctoral candidate in the UA's Department of Molecular and Cellular Biology. She worked under the direction of Henk Granzier, a professor in cellular and molecular medicine and physiology, who has studied titin for years.

Previous studies had shown that alterations in titin are involved in muscular myopathies, but whether these deviations actually cause myopathies, or merely result from them, has remained a mystery.

Buck has shown that mutations in the titin gene do in fact cause myopathies in skeletal muscles. Her study, published today in the Journal of General Physiology, could be an important first step in developing treatments to address causes of the disease.

"Patients with muscle myopathy experience muscle weakness, but not a lot has been known about what is going wrong at the molecular and genetic level, except that titin is often involved," Buck said. "Many patients with heart disease also have mutations in titin. So to develop treatments we need to understand the structure of titin and how it can cause or respond to disease."

"With about 35,000 amino acids, titin is the largest protein known, roughly 100 times larger than typical proteins, which have only around several hundred amino acids," Granzier explained. Amino acids are the building blocks of proteins.

Titin, he said, functions as a molecular spring that makes tissues elastic so that when they deform they can snap back again. "Titin is a vital determinant of the elasticity of skeletal and heart muscles, which is ver
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Contact: Shelley Littin
littin@email.arizona.edu
319-541-1482
University of Arizona
Source:Eurekalert  

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