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Narcolepsy gene identified

August 5, 1999 — Researchers who had bred a group of mice in hopes of learning more about a brain hormone that stimulates appetite got a bit of a surprise when they saw that the rodents would suddenly collapse and fall fast asleep with no provocation. As a result, Howard Hughes Medical Institute investigator Masashi Yanagisawa and colleagues at the University of Texas Southwestern Medical Center in Dallas have an exciting new lead into the genesis of sleep and the origins of narcolepsy, a severe sleep disorder in humans.

In 1998, Yanagisawa discovered the orexins, small brain proteins and their receptors that regulate feeding behavior in mice. To probe the role that orexins play in regulating appetite, Yanagisawa and his colleagues developed a strain of knockout mice whose orexin genes do not function properly. After raising several generations of the mice, the investigators videotaped the animals as they went about their daily business, hoping to see how the genetic alteration changed their behavior.

After scrutinizing hundreds of videotapes of mice scampering, grooming, eating, and sleeping, Richard Chemelli, a pediatric research fellow in Yanagisawa’s laboratory, began to feel discouraged because despite months of observation, the knockout mice did not seem any different from their normal, or wild-type, counterparts.

"Then we thought, wait a minute, mice are nocturnal. So watching them during the day is the equivalent of watching human behavior in the middle of the night. They're asleep," explained Yanagisawa. "So we started videotaping them in complete darkness using an infrared camcorder."

Chemelli studied nocturnal surveillance tapes of about 50 knockout mice and began to notice a bizarre and unexpected pattern of behavior. "The mice would be running around, burrowing, grooming themselves. Then all of a sudden, like a switch flipping, they w
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
6-Aug-1999


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