title: High amplitude phase resetting in rev-erbalpha/per1 double mutant mice.
abstract: Over time, organisms developed various strategies to adapt to their environment. Circadian clocks are thought to have evolved to adjust to the predictable rhythms of the light-dark cycle caused by the rotation of the Earth around its own axis. The rhythms these clocks generate persist even in the absence of environmental cues with a period of about 24 hours. To tick in time, they continuously synchronize themselves to the prevailing photoperiod by appropriate phase shifts. In this study, we disrupted two molecular components of the mammalian circadian oscillator, Rev-Erbalpha and Period1 (Per1). We found that mice lacking these genes displayed robust circadian rhythms with significantly shorter periods under constant darkness conditions. Strikingly, they showed high amplitude resetting in response to a brief light pulse at the end of their subjective night phase, which is rare in mammals. Surprisingly, Cry1, a clock component not inducible by light in mammals, became slightly inducible in these mice. Taken together, Rev-Erbalpha and Per1 may be part of a mechanism preventing drastic phase shifts in mammals.
authors.affiliation: Department of Medicine, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Corinne
authors.initials: C
authors.lastname: Jud
authors.forename: Antoinette
authors.initials: A
authors.lastname: Hayoz
authors.forename: Urs
authors.initials: U
authors.lastname: Albrecht
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000528:radiation effects; D003624:Darkness; D005260:Female; D008027:Light; D008297:Male; D051379:Mice / Q000235:genetics / Q000502:physiology*; D008810:Mice, Inbred C57BL; D009154:Mutation; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics* / Q000378:metabolism*; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C498262:Nr1d1 protein, mouse; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins
references.citation: Nat Rev Genet. 2008 Oct;9(10):764-75
references.pmid: 18802415
references.citation: Cell. 2002 Jul 26;110(2):251-60
references.pmid: 12150932
references.citation: Neuron. 2000 Feb;25(2):437-47
references.pmid: 10719897
references.citation: J Comp Neurol. 1972 Sep;146(1):1-14
references.pmid: 4116104
references.citation: Cell. 1993 Apr 23;73(2):279-94
references.pmid: 8097432
references.citation: Nature. 2000 Mar 2;404(6773):87-91
references.pmid: 10716448
references.citation: Biol Proced Online. 2005;7:101-16
references.pmid: 16136228
references.citation: Cell. 1999 Jan 8;96(1):57-68
references.pmid: 9989497
references.citation: Science. 2006 Jun 23;312(5781):1809-12
references.pmid: 16794082
references.citation: J Theor Biol. 1970 Sep;28(3):327-74
references.pmid: 5487648
references.citation: Genes Dev. 2002 Oct 15;16(20):2633-8
references.pmid: 12381662
references.citation: Proc Natl Acad Sci U S A. 1972 Jun;69(6):1583-6
references.pmid: 4556464
references.citation: Nature. 1999 Apr 15;398(6728):627-30
references.pmid: 10217146
references.citation: Mol Cell Biol. 2001 Nov;21(21):7287-94
references.pmid: 11585911
references.citation: Cell. 1999 Jul 23;98(2):193-205
references.pmid: 10428031
references.citation: EMBO J. 2001 Dec 17;20(24):7128-36
references.pmid: 11742989
references.citation: Science. 1999 Dec 24;286(5449):2531-4
references.pmid: 10617474
references.citation: Nat Neurosci. 1998 Dec;1(8):701-7
references.pmid: 10196586
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4106-11
references.pmid: 15024110
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9327-32
references.pmid: 16754844
references.citation: Eur J Neurosci. 2002 Oct;16(8):1531-40
references.pmid: 12405967
references.citation: Neuron. 2004 Aug 19;43(4):527-37
references.pmid: 15312651
references.citation: Nat Struct Mol Biol. 2005 May;12(5):441-8
references.pmid: 15821743
references.citation: Science. 1990 Feb 23;247(4945):975-8
references.pmid: 2305266
references.citation: Cell. 2001 Jun 1;105(5):683-94
references.pmid: 11389837
references.citation: Cell. 1997 Dec 26;91(7):1055-64
references.pmid: 9428527
references.citation: Aerosp Med. 1969 Aug;40(8):844-9
references.pmid: 5803983
references.citation: Cold Spring Harb Symp Quant Biol. 1960;25:159-84
references.pmid: 13736116
references.citation: Endocr Rev. 1999 Oct;20(5):689-725
references.pmid: 10529899
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14712-7
references.pmid: 17785416
references.citation: J Biol Rhythms. 2001 Apr;16(2):100-4
references.pmid: 11302552
references.citation: Genes Dev. 2003 Jun 1;17(11):1366-79
references.pmid: 12782655
references.citation: Nature. 2002 Aug 1;418(6897):534-9
references.pmid: 12152080
references.citation: Science. 1999 Oct 22;286(5440):768-71
references.pmid: 10531061