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Fruit fly gene combats wasting disorder. (Molecular Biology).

A gene regulating muscle formation in fruit flies could play a vitally important role in a wasting disorder in humans, researchers at the University of Texas Southwestern Medical Center at Dallas have discovered. "This study illustrates the way in which dissecting a basic problem in developmental biology can lead to unexpected connections to human disease," notes Eric Olson, chairman of molecular biology and senior author of the study.

"Who could have ever anticipated that studying an ancient gene that regulates muscle development in fruit flies could provide a window into understanding a wasting disorder in humans? That's really the beauty of biology and one of the gratifying aspects of this project for us."

Olson and his colleagues are examining the evolutionary conservation of developmental mechanisms, focusing specifically on muscle development and how a gene in a fruit fly can play the same function in a mouse. One gene, known as twist, encodes a gene-regulatory protein controlling muscle formation in fruit flies, and the researchers' initial hypothesis was that the function of the gene in both organisms would be identical.

After four years of study, however, the researchers found otherwise. Unexpectedly, mice genetically engineered to lack twist were underweight, frail, and developed cachexia, a severe wasting disorder that is commonly associated with cancer, AIDS, and chronic infection in humans. "The role of twist as a regulator of muscle development had been well-established in fruit flies by several groups, including our own, but the functions of the mammalian gene were not known," says Olson. "We assumed it would play a role similar to the fruit fly gene in controlling muscle development, but what we discovered was a completely unanticipated function for this ancient gene."

In the most-recent study, twist's connection with cachexia continues that battle against debilitating diseases. According to the National Association of Veterans' Research and Education Foundations, cachexia affects about half of all cancer and HIV patients, as well as those that have bacterial and parasitic diseases, chronic disorders, and rheumatoid arthritis of the bowel, liver, lungs, and heart.

Cachexia is triggered by cytokines, a family of circulating proteins. The researchers found that mice lacking twist showed highly elevated levels of cytokines because twist normally binds to the cytokine genes' control regions and then shuts them off. The absence of twist means the cytokines cannot be turned off. Instead, they become overexpressed, eventually leading to cachexia, Olson indicates.

James Richardson, professor of molecular biology and pathology and a study author, suggests the discovery that twist down-regulates certain cytokine pathways is important, as cytokines are also involved in chronic inflammatory diseases such as arthritis and asthma, and have been implicated in neuro-degenerative diseases. "Understanding the role of twist in the negative regulation of proinflammatory cytokines offers opportunities to design drugs to modulate cytokine expression in man."
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Publication:USA Today (Magazine)
Geographic Code:1USA
Date:Jun 1, 2003
Previous Article:Tiny molecules control life processes. (Microbiology).
Next Article:Plastics may cause birth defects. (Genetics).

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