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Easily paralyzed flies provide clues to neurodegeneration

MADISON - With a slight tweak of temperature, geneticist Barry Ganetzky's flies drop like, well, flies.

For 25 years, Ganetzky has been identifying, breeding and studying a raft of fly mutants that, when exposed to minor temperature change, become completely paralyzed. The flies, which quickly recover when returned to room temperature, are now finding many uses in studies of human neurological disorders, drug discovery and insecticide development.

Ganetzky, a University of Wisconsin-Madison professor of genetics, and his colleagues have become the undisputed champions of finding such mutants, raising the tally to upward of 100 such strains over the years.

"At room temperature, they are almost indistinguishable from normal flies," says Ganetzky of the genetic variants of the fly species Drosophila melanogaster, a workhorse of modern genetics and molecular biology. But if you expose them to slightly elevated temperatures in the range of human body temperature, "in less than 10 seconds, some mutants are completely paralyzed. Others become totally incapacitated by convulsive seizures. It's like flipping a switch. All we change is one variable - temperature."

The effect is a rapid loss of normal motor activity.

Such a handy model, Ganetzky explains, has tremendous potential for studies of disorders such as epilepsy, muscular dystrophies and a range of other neuromuscular disorders. What's more, the flies promise a window to identifying genes - many of which have human counterparts - involved in neural function and disease.

"Because the molecular mechanisms of neural function are highly conserved, whatever we learn from studying flies is likely to have important implications for humans as well," says Ganetzky.

The flies' sensitivity to temperature provides a unique ability to control the onset of their physiological d
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Contact: Barry Ganetzky
ganetzky@wisc.edu
608-263-2404
University of Wisconsin-Madison
4-Dec-2003


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