Photic Induction of
 mPer1
 and
 mPer2
 in
 Cry
 -Deficient Mice Lacking a Biological Clock

Okamura, Hitoshi; Miyake, Shigeru; Sumi, Yasuo; Yamaguchi, Shun; Yasui, Akira; Muijtjens, Manja; Hoeijmakers, Jan H.J.; Horst, Gijsbertus T. J. van der

doi:10.1126/science.286.5449.2531

Cited by 349 publications

(211 citation statements)

References 34 publications

Supporting

Mentioning

192

Contrasting

Unclassified

Order By: Relevance

“…In the PVN, PVT and DMH, the highest levels of Cry1 were observed at night, while those of Dbp, a clock-controlled gene, were observed a few hours earlier (except for DMH in which Dbp is not cycling), following comparable phase relationships in expression of the two genes within the SCN clock (Okamura et al, 1999;Yan et al, 2000).…”

Section: Circadian Oscillations In the Forebrain Of Mice Fed Ad Libitummentioning

confidence: 94%

“…Here we used a riboprobe for mCry1 (GenBank accession number AF156986) and mDbp (GenBank accession number NM016974). Cry1 was chosen as phase marker because its rhythmic expression is known to be more reliable than that of other clock genes such as Cry2 (Kume et al, 1999;Okamura et al, 1999). mDbp is a clock-controlled gene coding for a transcription factor called albumin D-site binding protein (DBP) whose transcription shows robust daily oscillations in the SCN (Lopez-Molina et al, 1997;Yan et al, 2000).…”

Section: Experimental Design For In Situ Hybridizationmentioning

confidence: 99%

See 1 more Smart Citation

Forebrain oscillators ticking with different clock hands

Feillet

Mendoza

Albrecht

et al. 2008

Molecular and Cellular Neuroscience

133

113

View full text Add to dashboard Cite

Clock proteins like PER1 and PER2 are expressed in the brain, but little is known about their functionality outside the main suprachiasmatic clock. Here we show that PER1 and PER2 were neither uniformly present nor identically phased in forebrain structures of mice fed ad libitum. Altered expression of the clock gene Cry1 was observed in respective Per1 or Per2 mutants. In response to hypocaloric feeding, PERs timing was not markedly affected in few forebrain structures (hippocampus). In most other forebrain oscillators, including those expressing only PER1 (e.g., dorsomedial hypothalamus), PER2 (e.g., paraventricular hypothalamus) or both (e.g., paraventricular thalamus), PER1 was up-regulated and PER2 largely phase-advanced. Cry1 expression was selectively modified in the forebrain of Per mutants challenged with hypocaloric feeding. Our results suggest that there is not one single cerebral clock, but a system of multiple brain oscillators ticking with different clock hands and differentially sensitive to nutritional cues.

show abstract

Section: Circadian Oscillations In the Forebrain Of Mice Fed Ad Libitummentioning

confidence: 94%

Section: Experimental Design For In Situ Hybridizationmentioning

confidence: 99%

Forebrain oscillators ticking with different clock hands

Feillet

Mendoza

Albrecht

et al. 2008

Molecular and Cellular Neuroscience

133

113

View full text Add to dashboard Cite

show abstract

“…For instance, the expression of Per1 and Per2, two "clock" genes often used as state variables of the molecular circadian clock, is decreased in Clock mutant mice (Oishi et al, 2000;Ripperger et al, 2000) and increased in Cry1,2 Ϫ/Ϫ mice (Griffin et al, 1999;Okamura et al, 1999;Vitaterna et al, 1999). Even the sleep abnormalities in mice lacking Dbp might be associated with reduced Per expression because, at least in vitro, DBP can amplify the CLOCK:BMAL1-induced Per transcription (Yamaguchi et al, 2000).…”

Section: Conclusion Sleep Homeostasis As An Oscillatory Network Of Trmentioning

confidence: 99%

Perchance to dream: Solving the mystery of sleep through genetic analysis

Shaw

Franken

2002

J. Neurobiol.

View full text Add to dashboard Cite

Sleep has been identified in all mammals and nonmammalian vertebrates that have been critically evaluated. In addition, sleep-like states have also been identified and described in several invertebrates. Despite this prevalence throughout the animal kingdom, the function of sleep remains a mystery. The completion of several genome sequencing projects has led to the expectation that fundamental aspects of sleep can be elucidated through genetic dissection. Indeed, studies in both the mouse and fly have begun to reveal tantalizing suggestions about the underlying principles that regulate sleep homeostasis. In this article we will review recent studies that have used genetic techniques to evaluate sleep in the fruit fly and the mouse.

show abstract

“…[41][42][43][44] The negative feedback loop involves rhythmic inhibition of the transcriptional activity of CLOCK/BMAL1 by the PER and CRY complexes. [45][46][47][48] These negative regulators also suppress the expression of REV-ERBa which inhibits BMAL1 transcription through RORE elements in the BMAL1 promoter. 49,50 Another component of the feedback loop involves DEC1 and DEC2 which repress BMAL1/CLOCK-induced gene transcription, 51 and their functions as clock-controlled genes has also been revealed.…”

Section: Introductionmentioning

confidence: 99%

Assessment of circadian function in fibroblasts of patients with bipolar disorder

et al. 2008

View full text Add to dashboard Cite

Previous studies have implicated the circadian system in the pathophysiology of bipolar disorder, but conclusive evidence for altered circadian clocks is lacking. Cultured fibroblasts harbor circadian clocks representative of those in the master clock resident in the suprachiasmatic nuclei, providing a new avenue to investigate the core clock machinery in patients with bipolar illness. We examined the rhythmic expression patterns of core clock genes (BMAL1, PER1, PER2, REV-ERBa, DEC2, DBP) in fibroblasts from 12 bipolar patients and 12 healthy controls. Although we did not detect differences in the circadian period between bipolar patients and controls, the amplitude of rhythmic expression for BMAL1, REVERBa and DBP, as well as the overall mRNA expression level for DEC2 and DBP was reduced in fibroblasts from bipolar patients. Bonferroni's correction for multiple comparisons still resulted in significantly reduced DBP expression level, and trends toward reduced overall expression level of DEC2 and circadian amplitude of BMAL1, in fibroblasts from bipolar patients. We next examined an expanded cohort of 18 bipolar patients and 35 healthy controls for mRNA expression levels of four kinases (CKId, CKIe, GSK3a and GSK3b) and the protein and phosphorylation levels of two of them (GSK3a and GSK3b). We did not detect differences in steady-state mRNA levels or protein levels of these kinases between bipolar patients and controls, but the level of GSK3b phosphorylation was significantly reduced in bipolar patients within an Old Order Amish bipolar kindred. Our results suggest that the reduced amplitudes and overall expression levels of circadian genes, and the decreased phosphorylation level of GSK3b may lead to dysregulation of downstream genes, which could explain some pathological features of bipolar disorder.

show abstract

Photic Induction of mPer1 and mPer2 in Cry -Deficient Mice Lacking a Biological Clock

Cited by 349 publications

References 34 publications

Forebrain oscillators ticking with different clock hands

Forebrain oscillators ticking with different clock hands

Perchance to dream: Solving the mystery of sleep through genetic analysis

Assessment of circadian function in fibroblasts of patients with bipolar disorder

Contact Info

Product

Resources

About