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The Journal of Neuroscience, November 8, 2006, 26(45):11615-11623; doi:10.1523/JNEUROSCI.3679-06.2006

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Behavioral/Systems/Cognitive
Attenuated Circadian Rhythms in Mice Lacking the Prokineticin 2 Gene

Jia-Da Li,¹ Wang-Ping Hu,¹ Lisa Boehmer,² Michelle Y. Cheng,¹ Alex G. Lee,¹ Alexander Jilek,³ Jerome M. Siegel,² and Qun-Yong Zhou¹

¹Department of Pharmacology, University of California, Irvine, Irvine, California 92697, ²Neurobiology Research 151A3, Veterans Administration Greater Los Angeles Healthcare System Sepulveda, Department of Psychiatry and Brain Research Institute, University of California, Los Angeles, School of Medicine, North Hills, California 91343, and ³Institute of Organic Chemistry, Johannes-Kepler-University, 4040 Linz, Austria

Correspondence should be addressed to Qun-Yong Zhou, Department of Pharmacology, University of California, Irvine, Irvine, CA 92697. Email: qzhou{at}uci.edu

Circadian clocks drive daily rhythms in virtually all organisms. In mammals, the suprachiasmatic nucleus (SCN) is recognized as the master clock that synchronizes central and peripheral oscillators to evoke circadian rhythms of diverse physiology and behavior. How the timing information is transmitted from the SCN clock to generate overt circadian rhythms is essentially unknown. Prokineticin 2 (PK2), a clock-controlled gene that encodes a secreted protein, has been indicated as a candidate SCN clock output signal that regulates circadian locomotor rhythm. Here we report the generation and analysis of PK2-null mice. The reduction of locomotor rhythms in PK2-null mice was apparent in both hybrid and inbred genetic backgrounds. PK2-null mice also displayed significantly reduced rhythmicity for a variety of other physiological and behavioral parameters, including sleep–wake cycle, body temperature, circulating glucocorticoid and glucose levels, as well as the expression of peripheral clock genes. In addition, PK2-null mice showed accelerated acquisition of food anticipatory activity during a daytime food restriction. We conclude that PK2, acting as a SCN output factor, is important for the maintenance of robust circadian rhythms.

Key words: circadian rhythm; prokineticin 2; knock-out; suprachiasmatic nucleus; sleep; locomotor

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Received Aug. 23, 2006; revised Sept. 27, 2006; accepted Oct. 2, 2006.

Correspondence should be addressed to Qun-Yong Zhou, Department of Pharmacology, University of California, Irvine, Irvine, CA 92697. Email: qzhou{at}uci.edu

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