Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Casein kinase 1 delta regulates the pace of the mammalian circadian clock.

http://www.ncbi.nlm.nih.gov/pubmed/19414593

Both casein kinase 1 delta (CK1delta) and epsilon (CK1epsilon) phosphorylate core clock proteins of the mammalian circadian oscillator. To assess the roles of CK1delta and CK1epsilon in the circadian clock mechanism, we generated mice in which the genes encoding these proteins (Csnk1d and Csnk1e, respectively) could be disrupted using the Cre-loxP system. Cre-mediated excision of the floxed exon 2 from Csnk1d led to in-frame splicing and production of a deletion mutant protein (CK1delta(Delta2)). This product is nonfunctional. Mice homozygous for the allele lacking exon 2 die in the perinatal period, so we generated mice with liver-specific disruption of CK1delta. In livers from these mice, daytime levels of nuclear PER proteins, and PER-CRY-CLOCK complexes were elevated. In vitro, the half-life of PER2 was increased by approximately 20%, and the period of PER2::luciferase bioluminescence rhythms was 2 h longer than in controls. Fibroblast cultures from CK1delta-deficient embryos also had long-period rhythms. In contrast, disruption of the gene encoding CK1epsilon did not alter these circadian endpoints. These results reveal important functional differences between CK1delta and CK1epsilon: CK1delta plays an unexpectedly important role in maintaining the 24-h circadian cycle length.

Pubmed ID: 19414593 RIS Download

Mesh terms: Animals | Base Sequence | CLOCK Proteins | Casein Kinase Idelta | Casein Kinase Iepsilon | Cell Cycle Proteins | Cells, Cultured | Circadian Rhythm | Cryptochromes | DNA Primers | Female | Fibroblasts | Flavoproteins | Half-Life | Liver | Male | Mice | Mice, Inbred C57BL | Mice, Knockout | Mice, Transgenic | Nuclear Proteins | Period Circadian Proteins | Trans-Activators | Transcription Factors

Research resources used in this publication

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIDDK NIH HHS, Id: DK32520
  • Agency: NIGMS NIH HHS, Id: F32 GM074277
  • Agency: NINDS NIH HHS, Id: R01 NS047141
  • Agency: NINDS NIH HHS, Id: R01 NS056125
  • Agency: NINDS NIH HHS, Id: R01 NS056125
  • Agency: NINDS NIH HHS, Id: R01 NS056125-03
  • Agency: NINDS NIH HHS, Id: R01 NS056125-04
  • Agency: NINDS NIH HHS, Id: R21 NS051458
  • Agency: NINDS NIH HHS, Id: R21 NS051458-02
  • Agency: NINDS NIH HHS, Id: R21NS051458

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.