The Narcolepsy Gene and Man's Best Friend

By Ellen Kuwana
Neuroscience for Kids Staff Writer
March 4, 2000

Narcolepsy

Narcolepsy is a sleep disorder that disrupts both the onset of sleep and the sleep cycle, including REM sleep. Because it is difficult to study human sleep behavior and physiology, researchers have turned to other mammals that have narcolepsy.

Clues from Man's Best Friend

Stanford University's Sleep Clinic has a colony of dogs that have narcolepsy. Researchers, led by Emmanuel Mignot, PhD, have found that these dogs have the gene for narcolepsy. They used a technique called positional cloning and published their results in the August 6, 1999 issue of the journal called Cell.

Positional Cloning

Briefly, positional cloning starts by isolating DNA from a blood sample. This does not harm the donor (in this case, the dog). DNA is made up of building blocks called nucleotides (just like a necklace is made up of links or beads). There are four nucleotides, called A, T, G, and C. The Stanford scientists compared the patterns of these nucleotides to look for differences between healthy dogs and dogs with narcolepsy. The scientists identified a unique region (marker) within individuals that allowed them to track the disease with the marker. This is called linkage analysis. Then the researchers searched for the disease gene near that marker. This approach identified the narcolepsy gene.

The scientists dubbed the gene hypocretin receptor 2 . This gene carries the instructions to make a protein that acts like an antenna on certain cells, picking up messages from other cells. Because the gene is defective in narcoleptic dogs, the hypocretin signal is not received by these cells. Therefore, the neurons that they connect to are not stimulated appropriately. This may be one reason why signals that tell the brain and body to be awake and alert go unheeded in individuals with narcolepsy. It was already known that hypocretins play a role in feeding behavior, but their role in arousal was a surprise.

But What Does this Mean for Humans?

Dr. Mignot and others know that a similar gene exists in humans, so the task is to find the defective human gene or genes that cause narcolepsy. While this is not of immediate help to narcoleptics, knowledge about how sleep works may help treat sleep disorders. Not only could this information lead to drugs which promote wakefulness, it could also influence how medications to help people sleep are made in the future.

References:

  1. Narcolepsy Gene Found
  2. "Narcolepsy Genes Wake Up the Sleep Field," by Joseph Takahashi, Science, September 24, 1999, pp. 2076-77.
  3. Lin, L. Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X., Qiu, X., de Jong, P.J., Nishino, S., Mignot, E. "The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell, 1999 August 6; 98 (3):365-76.

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