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Genetically-engineered 'marathon mouse' keeps on running

By enhancing the function of a single protein, Howard Hughes Medical Institute researchers have produced a "marathon mouse" with altered muscle composition and enough physical endurance to run twice as far as normal mice. Mice with the enhanced protein also showed an innate resistance to weight gain, even when fed a high-fat diet that caused normal mice to become obese.

According to the researchers, their finding will offer important insights into the machinery that powers muscle development and the physiological changes produced by exercise. The finding also suggests a route to designing drugs that enhance muscle development and mimic all the benefits of exercise. The researchers said such drugs could aid patients whose debilitating diseases prevent them from exercising. The researchers recognize that such drugs already being tested by pharmaceutical companies could be abused as a way to enhance athletic performance.

Led by Howard Hughes Medical Institute investigator Ronald M. Evans at The Salk Institute, the researchers published their findings online August 24, 2004, in the journal Public Library of Science Biology. Other co-authors are from Seoul National University in Korea.

In their studies, the researchers were exploring the effects of altering the gene for a protein called PPAR-delta -- a master regulator of numerous genes -- to enhance that protein's activity. According to Evans, they had not expected the profound and far-reaching physiological effects of this single genetic alteration.

"In previous work, we had shown that in various tissues, particularly adipose tissues, activating PPAR-delta increased fat burning and, as a result, decreased fat-tissue mass," said Evans. "Going into this experiment, the possibility of an effect on muscle fibers was not on our radar screen."

However, when the researchers produced mice with enhanced PPAR-delta activity, they saw a major transformation in skeletal muscle fibers. The mic
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
23-Aug-2004


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