Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock.
The role of mPer1 and mPer2 in regulating circadian rhythms was assessed by disrupting these genes. Mice homozygous for the targeted allele of either mPer1 or mPer2 had severely disrupted locomotor activity rhythms during extended exposure to constant darkness. Clock gene RNA rhythms were blunted in the suprachiasmatic nucleus of mPer2 mutant mice, but not of mPER1-deficient mice. Peak mPER and mCRY1 protein levels were reduced in both lines. Behavioral rhythms of mPer1/mPer3 and mPer2/mPer3 double-mutant mice resembled rhythms of mice with disruption of mPer1 or mPer2 alone, respectively, confirming the placement of mPer3 outside the core circadian clockwork. In contrast, mPer1/mPer2 double-mutant mice were immediately arrhythmic. Thus, mPER1 influences rhythmicity primarily through interaction with other clock proteins, while mPER2 positively regulates rhythmic gene expression, and there is partial compensation between products of these two genes.
Bae
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Laboratory of Developmental Chronobiology, MassGeneral Hospital for Children, Massachusetts General Hospital, and, Harvard Medical School, 02114, Boston, MA, USA
Jin
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Maywood
E S
ES
Hastings
M H
MH
Reppert
S M
SM
Weaver
D R
DR
D000818:Animals; D001683:Biological Clocks; D001921:Brain / Q000378:metabolism; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000235:genetics*; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D015698:Genomic Library; D005838:Genotype; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D056950:Period Circadian Proteins; D010507:Periodicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D014157:Transcription Factors; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; C512645:Per3 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors