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Science 301 (5631): 379-383

Copyright © 2003 by the American Association for the Advancement of Science

Altered Patterns of Sleep and Behavioral Adaptability in NPAS2-Deficient Mice

Carol A. Dudley,1 Claudia Erbel-Sieler,1 Sandi Jo Estill,1 Martin Reick,1 Paul Franken,2 SiNae Pitts,3 Steven L. McKnight1*

Abstract: Animal behavior is synchronized to the 24-hour light:dark (LD) cycle by regulatory programs that produce circadian fluctuations in gene expression throughout the body. In mammals, the transcription factor CLOCK controls circadian oscillation in the suprachiasmatic nucleus of the brain; its paralog, neuronal PAS domain protein 2 (NPAS2), performs a similar function in other forebrain sites. To investigate the role of NPAS2 in behavioral manifestations of circadian rhythm, we studied locomotor activity, sleep patterns, and adaptability to both light- and restricted food–driven entrainment in NPAS2-deficient mice. Our results indicate that NPAS2 plays a substantive role in maintaining circadian behaviors in normal LD and feeding conditions and that NPAS2 is critical for adaptability to food restriction.

1 Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390–9152, USA. 2 Department of Biological Sciences, Stanford University, Stanford, CA 94305–5020, USA. 3 Department of Psychology, Columbia University, 1190 Amsterdam Avenue, New York, NY 10027, USA.

* To whom correspondence should be addressed. E-mail: smckni{at}

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