On Aug. 11, 1999, researchers led by Stanford’s Emmanuel Mignot, MD, PhD, associate professor of psychiatry, used a technique called positional cloning to pinpoint the gene in dogs, one of the few species besides humans known to develop narcolepsy.

The researchers, led by Emmanuel Mignot, MD, PhD, associate professor of psychiatry at Stanford University School of Medicine, used a technique called positional cloning to pinpoint the gene in dogs, one of the few species besides humans known to develop narcolepsy. Mignot predicts the finding will not only help the roughly 135,000 Americans who suffer from narcolepsy, but in time it will shed light on two of the biggest mysteries in sleep research: how and why we sleep..

“Narcolepsy is the only known neurological disorder that affects the brain and sleep in such a dramatic way,” said Mignot, who is director of Stanford’s Center for Narcolepsy. It affects both humans and animals and has both genetic and sporadic forms. Usually beginning in adolescence, narcolepsy’s symptoms include extreme daytime sleepiness, sleep paralysis – a frightening inability to move shortly after awakening or shortly after dozing off – as well as vivid auditory or visual hallucinations while asleep or while falling asleep.

In the August 6 issue of Cell, Mignot and his colleagues report locating two defective versions of the narcolepsy gene, one in Doberman pinschers, the other in Labrador retrievers. The gene, known as hypocretin receptor 2, codes for a protein that juts out from the surface of brain cells and that functions as an antenna, allowing the cell to receive messages – transmitted via small molecules called hypocretins – from other cells. The defective versions of the gene encode proteins that cannot recognize these messages, in effect cutting the cell off from essential directives, including perhaps messages that promote wakefulness.

In people, the situation is much more complicated. While the disorder occasionally runs in families, most narcoleptics have no affected relatives. Mignot said the inheritance of human narcolepsy resembles diseases like heart disease and diabetes, in which several genes contribute to susceptibility but the disorder usually will not develop without a specific environmental trigger.