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:
- Narcolepsy Gene Found
- "Narcolepsy Genes Wake Up the Sleep Field," by Joseph Takahashi,
Science, September 24, 1999, pp. 2076-77.
- 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.