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Discovery: Experiments Confirm Novel Eye Pigment Controls Circadian Rhythm

CHAPEL HILL - New research by University of North Carolina at Chapel Hill scientists has proven that a light-sensitive pigment they discovered in the eye, the skin and part of the brain controls the body's internal clock.

Their initial discovery, published in May, was the first of its kind in more than a century. The work could lead to better treatment for depression and fewer accidents during night work shifts, researchers say.

"Because some investigators questioned how conclusive our earlier data was, we decided to create a mouse lacking the pigment to see what effect it had on the mouse," said Dr. Aziz Sancar, Kenan professor of biochemistry and biophysics at the UNC-CH School of Medicine. "Using what some people have called 'knock-out mouse technology,' we created animals that lacked the gene responsible for making the pigment."

The scientists found the pigment, called cryptochrome (CRY), drives mammals' circadian rhythm, the 24-hour biological timer that regulates numerous bodily functions, Sancar said. Those processes -- synchronized to light and dark by light at dawn -- range from body temperature and blood pressure regulation to intellectual performance, sleep and wakefulness.

A report on the findings appears in the Nov. 20 issue of Science. Besides Sancar, authors are Randy J. Thresher, Yasuhide Miyamoto, Aleksey Kazantsev, David S. Hsu, Claude Petit, Christopher P. Selby, Lala Dawut and Oliver Smithies, all of UNC-CH, and Martha Hotz Vitatarna and Joseph S. Takahashi of Northwestern University.

Experiments at UNC-CH showed that production of a protein known as "Period," which is controlled by light and helps regulate mammals' internal clock, was reduced by more than 50 percent in the mutant mice, Sancar said.

Complementary experiments at Northwestern that involved having the Carolina knockout mice running on treadmills and resting during simulated nights and days showed mutants to
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Contact: David Williamson
David_Williamson@unc.edu
919-962-8596
University of North Carolina at Chapel Hill
19-Nov-1998


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