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Science 298 (5601): 2213-2216

Copyright © 2002 by the American Association for the Advancement of Science

Melanopsin (Opn4) Requirement for Normal Light-Induced Circadian Phase Shifting

Satchidananda Panda,12 Trey K. Sato,12 Ana Maria Castrucci,34 Mark D. Rollag,3 Willem J. DeGrip,5 John B. Hogenesch,1 Ignacio Provencio,3* Steve A. Kay12*

The master circadian oscillator in the hypothalamic suprachiasmatic nucleus is entrained to the day/night cycle by retinal photoreceptors. Melanopsin (Opn4), an opsin-based photopigment, is a primary candidate for photoreceptor-mediated entrainment. To investigate the functional role of melanopsin in light resetting of the oscillator, we generated melanopsin-null mice (Opn4-/-). These mice entrain to a light/dark cycle and do not exhibit any overt defect in circadian activity rhythms under constant darkness. However, they display severely attenuated phase resetting in response to brief pulses of monochromatic light, highlighting the critical role of melanopsin in circadian photoentrainment in mammals.

1 Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins Drive, San Diego, CA 92121, USA.
2 Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, San Diego, CA 92037, USA.
3 Department of Anatomy, Physiology, & Genetics, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
4 Department of Physiology, University of Saõ Paolo, Post Office Box 11176, Saõ Paolo 05422, Brazil.
5 Department of Biochemistry, University of Nijmegen, Post Office Box 9101, 6500 HB Nijmegen, The Netherlands.
*   To whom correspondence should be addressed. E-mail: stevek{at}, provenci{at}

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