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Science 325 (5942): 866-870

Copyright © 2009 by the American Association for the Advancement of Science

The Transcriptional Repressor DEC2 Regulates Sleep Length in Mammals

Ying He,1 Christopher R. Jones,2 Nobuhiro Fujiki,3 Ying Xu,1,* Bin Guo,4 Jimmy L. Holder, Jr.,1,{dagger} Moritz J. Rossner,5 Seiji Nishino,3 Ying-Hui Fu1,{ddagger}

Abstract: Sleep deprivation can impair human health and performance. Habitual total sleep time and homeostatic sleep response to sleep deprivation are quantitative traits in humans. Genetic loci for these traits have been identified in model organisms, but none of these potential animal models have a corresponding human genotype and phenotype. We have identified a mutation in a transcriptional repressor (hDEC2-P385R) that is associated with a human short sleep phenotype. Activity profiles and sleep recordings of transgenic mice carrying this mutation showed increased vigilance time and less sleep time than control mice in a zeitgeber time– and sleep deprivation–dependent manner. These mice represent a model of human sleep homeostasis that provides an opportunity to probe the effect of sleep on human physical and mental health.

1 Department of Neurology, University of California at San Francisco, Mission Bay, 1550 Fourth Street, San Francisco, CA 94158, USA.
2 Department of Neurology, University of Utah, Salt Lake City, UT 84132, USA.
3 Sleep and Circadian Neurobiology Laboratory, Stanford University, 1201 Welch Road, P213, Palo Alto, CA 94304, USA.
4 Mechanical Engineering, University of California, Berkeley, Hesse Hall, Room 245, Berkeley, CA 94720, USA.
5 Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.

* Present address: Model Animal Resource Center, Nanjing University, China 210061.

{dagger} Present address: Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX 77030, USA.

{ddagger} To whom correspondence should be addressed. E-mail: ying-hui.fu{at}ucsf.edu


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