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dc.contributor.authorEtchegaray, Jean-Pierre
dc.contributor.authorMachida, Kazuhiko K.
dc.contributor.authorNoton, Elizabeth
dc.contributor.authorConstance, Cara M.
dc.contributor.authorDallmann, Robert
dc.contributor.authorDi Napoli, Marianne N.
dc.contributor.authorDeBruyne, Jason P.
dc.contributor.authorLambert, Christopher M.
dc.contributor.authorYu, Elizabeth A.
dc.contributor.authorReppert, Steven M.
dc.contributor.authorWeaver, David R.
dc.date2022-08-11T08:09:39.000
dc.date.accessioned2022-08-23T16:39:02Z
dc.date.available2022-08-23T16:39:02Z
dc.date.issued2009-05-06
dc.date.submitted2010-04-06
dc.identifier.citation<p>Mol Cell Biol. 2009 Jul;29(14):3853-66. Epub 2009 May 4. <a href="http://dx.doi.org/10.1128/MCB.00338-09">Link to article on publisher's site</a></p>
dc.identifier.issn0270-7306 (Linking)
dc.identifier.doi10.1128/MCB.00338-09
dc.identifier.pmid19414593
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39384
dc.description<p>Co-authors Kazuhiko K. Machida and Elizabeth A. Yu are students in the Neuroscience program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School. Elizabeth Yu is also in GSBS' MD/PhD Program.</p>
dc.description.abstractBoth 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=19414593&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704743/
dc.subjectAnimals
dc.subjectBase Sequence
dc.subjectCLOCK Proteins
dc.subjectCasein Kinase Idelta
dc.subjectCasein Kinase Iepsilon
dc.subjectCell Cycle Proteins
dc.subjectCells, Cultured
dc.subjectCircadian Rhythm
dc.subjectCryptochromes
dc.subjectDNA Primers
dc.subjectFemale
dc.subjectFibroblasts
dc.subjectFlavoproteins
dc.subjectHalf-Life
dc.subjectLiver
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectMice, Transgenic
dc.subjectNuclear Proteins
dc.subjectPeriod Circadian Proteins
dc.subjectTrans-Activators
dc.subjectTranscription Factors
dc.subjectNeuroscience and Neurobiology
dc.titleCasein kinase 1 delta regulates the pace of the mammalian circadian clock
dc.typeJournal Article
dc.source.journaltitleMolecular and cellular biology
dc.source.volume29
dc.source.issue14
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2180
dc.identifier.contextkey1262960
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/2180
dc.contributor.departmentGraduate School of Biomedical Sciences, MD/PhD Program
dc.contributor.departmentGraduate School of Biomedical Sciences, Neuroscience Program
dc.contributor.departmentWeaver Lab
dc.contributor.departmentReppert Lab
dc.contributor.departmentNeurobiology
dc.source.pages3853-66
dc.contributor.studentElizabeth A. Yu
dc.contributor.studentKazuhiko K. Machida
dc.description.thesisprogramMD/PhD
dc.description.thesisprogramNeuroscience


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