The presumed genetic mainstays of research into the sleeping disorder known as narcolepsy looked as if they might be in the doghouse last year. That’s when investigators discovered that a group of missing brain cells–not a genetic mutation found in narcoleptic Doberman pinschers and Labrador retrievers–was at the heart of the disease in people (SN: 9/2/00, p. 148). New findings have given researchers something to chew on.
Dogs with the same sudden, uncontrollable bouts of sleepiness as people with narcolepsy have helped unlock secrets of the disease. Unlike human narcolepsy, the dogs’ disease is usually caused by a single gene mutation. Now evidence from studies with dachshunds and poodles is suggesting that these small breeds may serve as better models for the more genetically complex narcolepsy in people.
“This shows that there is another way to get the same genetics,” says Jerome M. Siegel of the University of California, Los Angeles. He’s the scientist who pinpointed the specific brain-cell destruction related to narcolepsy.
Narcolepsy affects an estimated 200,000 people in the United States alone. People who have narcolepsy become drowsy or fall asleep unexpectedly. They may also experience temporary paralysis, frightening hallucinations when falling asleep, or sudden losses of all muscle control while still conscious.
After sleep scientists first came across narcoleptic dogs, researchers bred the animals, analyzed their brains and brain chemicals, and found that simple genetic mutations could give the dogs all the symptoms of the disease (SN: 11/25/95, p. 356).
Researchers found that many of these animals had a mutated form of a gene called Hcrtr2, which codes for brain-cell receptors that interact with a protein called hypocretin (SN: 8/14/99, p. 148). Hypocretin promotes wakefulness, and dogs with defective hypocretin receptors have narcoleptic symptoms.
Tests of hundreds of narcoleptic people, however, turned up only one case of a similar genetic mutation. Most human cases are sporadic, meaning they don’t run in families, says Thomas Kilduff of SRI International Molecular Neurobiology Laboratory in Menlo Park, Calif.
In a study in the April Genome Research, Marcel Hungs and his coworkers at the Stanford University Medical Center examined dachshunds and poodles with sporadic cases of narcolepsy. They found that these dogs had intact copies of the Hcrtr2 gene, as do most people with narcolepsy.
“A few months ago, I thought the dogs may not be a good model,” says Kilduff. The new research shows that sporadic cases in dogs resemble narcolepsy in people, he concedes.
Mysteries remain, however. For example, although the gene for hypocretin receptors is intact in the dachshunds and poodles, some of these animals have undetectable concentrations of hypocretin in their cerebrospinal fluid.
Michael Twery of the National Center on Sleep Disorders Research at the National Institutes of Health in Bethesda, Md., says that these findings are part of a sea change in sleep research. “Sleep is currently defined in terms of brain activity measured in brainwaves,” he says. “This research reflects an effort to redefine sleep in chemical terms.”