DALLAS - August 6, 1999 - Using an infrared, nighttime video camera to study genetically engineered mice lacking a molecule known to affect appetite, UT Southwestern Medical Center at Dallas researchers unexpectedly discovered they had created a rodent with the sleep disorder narcolepsy.

This finding is significant because there is no cure or long-term treatment for the illness, which affects 200,000 Americans and can alter social, personal and professional activities because those suffering from it frequently fall asleep at inappropriate times. Knowing what causes narcolepsy could lead to treatments.

The research will be published in the Aug. 20 issue of Cell, but the journal lifted the embargo two weeks early because the Aug. 6 issue contains a related report.

The UT Southwestern scientists created the disorder in the mice when they removed the neuropeptide orexin to examine how removal of this protein, found in nerve cells of the brain's lateral hypothalamus, changed the animals' habits. They found that the mice unexpectedly fell asleep in the middle of high activity, said Dr. Masashi Yanagisawa, professor of molecular genetics and senior author of the study.

He and his colleagues last year discovered orexin-A and orexin-B, the ligands or keys, and OX1 and OX2, the receptors or locks, that fit together to begin an intercellular communication process that stimulates food consumption. The work that led to the narcoleptic mice was a continuation of the orexin research.

"During the course of our work, we decided that it was best to study the mice at night, which is when they are most active," said Yanagisawa, also a Howard Hughes Medical Institute (HHMI) investigator and holder of the Patrick E. Haggerty Distinguished Chair in Basic Biomedical Science.

In observing the rodents, Dr. Richard Chemelli, the lead author and a pediatric research fellow, noticed that the animals sometimes
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Contact: Susan Steeves
susan.steeves@email.swmed.edu
214-648-3404
UT Southwestern Medical Center
6-Aug-1999