Attenuated circadian rhythms in mice lacking the prokineticin 2 gene.
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.
Li
Jia-Da
JD
Department of Pharmacology, University of California, Irvine, Irvine, California 92697, USA.
Hu
Wang-Ping
WP
Boehmer
Lisa
L
Cheng
Michelle Y
MY
Lee
Alex G
AG
Jilek
Alexander
A
Siegel
Jerome M
JM
Zhou
Qun-Yong
QY
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001786:Blood Glucose / Q000235:genetics; D001831:Body Temperature / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics*; D003345:Corticosterone / Q000097:blood; D056931:Cryptochromes; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography / Q000379:methods; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D005508:Food Deprivation / Q000502:physiology; D005768:Gastrointestinal Hormones / Q000172:deficiency / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology; D009043:Motor Activity / Q000235:genetics; D009479:Neuropeptides / Q000172:deficiency / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012890:Sleep / Q000235:genetics; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D013997:Time Factors; D014851:Wakefulness / Q000235:genetics
D001786:Blood Glucose; D056931:Cryptochromes; D005420:Flavoproteins; D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C486586:Prok2 protein, mouse; D012333:RNA, Messenger; D003345:Corticosterone