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

y important for normal muscular function," he noted.

"Titin is like the stretchy material in a rubber balloon," said Buck. "If you have a balloon that is too stretchy or too stiff, then it's not going to be able to expand or contract. Tissues also need to have elasticity so that they can restore their original shape after they have been contracted."

Conducting genetic testing for mutations in the titin gene and studying the defects in the protein have been challenging due to titin's "enormous size," Granzier said. "But excellent facilities at the University of Arizona have enabled researchers to make great impact and progress has recently accelerated."

Buck's research "has directly shown that introducing specific changes to the titin gene can lead to disease in skeletal muscles," Granzier said. "We know now that titin itself can trigger the disease. Danielle's research shows that this giant protein needs to be tuned just right or it can cause myopathies to develop in skeletal muscles."

Buck's research "also demonstrated for the first time that changing a part of the gene results in a cascade of additional damaging changes in the protein," he added.

"We found that in skeletal muscles, deleting one area of titin can affect expression of the entire protein and other areas can subsequently be deleted as well," Buck said. "Shortening titin leads to a cascade of effects that cause titin to be even shorter, and that causes the muscle to become very stiff."

Buck approached her work from many levels, Granzier said. "She worked at the gene level, the transcription level, the protein level and the functional level of cells and tissues to get an integrative understanding of the changes that this genetic modification caused."

"We try to look at all these levels so that we can get a deeper understanding of the mechanisms that give rise to disease," he added. "It is a multidisciplinary study, from molecular and cellula
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Contact: Shelley Littin
littin@email.arizona.edu
319-541-1482
University of Arizona
Source:Eurekalert  

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