Circadian rhythm in Clock mutant and Cry deficient mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE454 | GEO | 2003/11/08
SECONDARY ACCESSION(S): PRJNA85053
REPOSITORIES: GEO
Similar Datasets
Project description:Molecular analysis of circadian rhythm in mice. Liver tissue of wildtype, Clock mutant and Cry deficient C57BL/6 8- to 10-week-old male mice examined.
2007-11-07 | E-GEOD-454 | biostudies-arrayexpress
Project description:Circadian rhythm in clock mutants
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Project description:The circadian system regulates numerous physiological processes including the adaptive immune system. Here we show that mice deficient for the circadian genes Cry1 and Cry2, (DKO) display an autoimmune phenotype including higher serum IgG concentration, presence of serum anti-nuclear antibodies, precipitation of IgG, IgM and complement 3 in glomeruli, and massive infiltrations of leukocytes into the lung and kidney. Activation of Cry DKO splenic B cells elicited markedly enhanced and prolonged tyrosine phosphorylation of cellular proteins compared to cells from control mice, suggesting that over activation of the BCR signaling pathway may contribute to autoimmunity in the Cry DKO mice. Expression of C1q, deficiency of which contributes to the pathogenesis of Systemic lupus erythematosus (SLE), was significantly downregulated in Cry DKO B cells. This suggests that B cell development, BCR signaling pathway and C1q expression may be under direct circadian control and dysregulation of which contributes to autoimmunity.
2018-08-24 | GSE87467 | GEO
Project description:One hundred ninety wildtype male C57BL/6J mice age 7-10 weeks were purchased from Jackson Laboratory and entrained to a 12:12 light:dark cycle for 2 weeks. Mice were placed in light-tight boxes on a 12:12 LD cycle for 4 weeks, then released into constant darkness. Starting 30 hours after entry into DD (CT18), tissues from 5 (skeletal muscle) or 10 (liver or SCN) wildtype mice were collected every 4 hours for 48 hours, for a total of 12 timepoints. At timepoints 34 through 58 hours in DD, tissues from age-matched male C57BL/6J Clock/Clock homozygous mutant mice that had been treated with the same light entrainment protocol as the wildtype were collected. Tissues were collected from 5 Clock/Clock mutants at each timepoint except for 34 and 46 hours after the onset of DD, when tissues from 10 Clock/Clock mice were collected and run as independent replicates. Mice were sacrificed by cervical dislocation, and the optic nerves were severed in complete darkness; brain dissection was performed using illumination from an infrared viewer (FJW Industries, Palatine, IL). SCNs were dissected out, pooled at a density of 5 per tube in 100 ul RNAlater (Ambion, Austin, TX), frozen on dry ice, and stored at â80 degrees C until use. Keywords: SuperSeries This reference Series links data in the following related Series: GSE3746 Circadian skeletal muscle_wt and Clock mutants GSE3748 Circadian liver_wt and Clock mutants
2010-06-12 | E-GEOD-3751 | biostudies-arrayexpress
Project description:The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK-BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK:BMAL1:CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized protein that directly interacts with BMAL1 and represses CLOCK:BMAL1 activity. In vitro and in vivo protein-DNA interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK:BMAL1 complex on DNA. Although Gm129-/- or Cry1-/- Gm129-/- mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit significant phase delay compared to control. Our results suggest that, in addition to CRYs and PERs, GM129 protein contributes to the transcriptional feedback loop by modulating CLOCK:BMAL1 activity as a transcriptional repressor. Examination of 3 transcriptional regulators in mouse liver
2014-01-07 | E-GEOD-53828 | biostudies-arrayexpress
Project description:The diurnal peak of phagocytosis by the retinal pigment epithelium (RPE) of photoreceptor outer segments is under circadian control, and it is believed that this process involves interactions from both the retina and RPE. Previous studies have demonstrated that a functional circadian clock exists within multiple retinal cell types and RPE cells. Thereby, the aim of the current study was to determine whether the circadian clock in the retina and or RPE controls the diurnal phagocytic peak of photoreceptor outer segments and whether selective disruption of the circadian clock in the RPE would affect RPE cells function and the viability during aging. To that aim, we first generated and validated an RPE tissue-specific KO of the essential clock gene, Bmal1, and then we determined the daily rhythm in phagocytic activity by the RPE in mice lacking a functional circadian clock in the retina or RPE. Then using electroretinography, spectral domain-optical coherence tomography, and optomotor response measurements of visual function we determined the effect of Bmal1 removal in young (6-month-old) and old (18-months old) mice. RPE morphology and lipofuscin accumulation was also determined in young and old mice. Our data show that the circadian clock in the RPE controls the daily diurnal phagocytic peak of POS. Surprisingly, the lack of a functional RPE circadian clock or the diurnal phagocytic peak does not result in any detectable age-related degenerative phenotype in the retina or RPE. Thus, our results demonstrate that the circadian clock in the RPE controls the daily peak in the phagocytic activity. However, the loss of the circadian clock in the RPE does not result in deterioration of photoreceptors or the RPE during aging.
2022-05-12 | GSE191104 | GEO
Project description:Circadian rhythms are a series of endogenous autonomous 24-hour oscillations generated by the circadian clock. At the molecular level, the circadian clock is generated by a transcription-translation feedback loop, where BMAL1 and CLOCK transcription factors of the positive arm activate the expression of CRYPTOCHROME and PERIOD (PER) genes of the negative arm as well as the circadian clock-regulated genes. In this project, we aimed at finding the interactome of PER2 protein in human U2OS osteosarcoma cell line using proximity-dependent biotin identification (BioID) technique. U2OS clones overexpressing PER2-BioID2 or BioID2 were treated with dexamethasone in order to reset the circadian rhythm, and cells were then incubated in biotin-containing media for 12 hours to label the proteins in close proximity of PER2-BioID2. Samples were collected after 36 and 48 hours of the resetting to identify the labeled proteins by mass spectrometry. In addition to known interactors such as CRY1 and CRY2, many novel interactors were identified. In summary, we obtained a network of PER2 interactome and confirmed some of the novel interactions using classical the co-immunoprecipitation method.
2022-04-22 | PXD025179 | Pride
Project description:Using larval zebrafish as a model system, we applied a genome-wide transcriptome approach that allowed us to investigate circadian gene expression that can be associated with various tissues and cell types. Our analysis of circadian gene regulatory network revealed a general principle: circadian clock controls diverse aspects of circadian physiology through transcriptional cascade of transcription factors (TFs). As a proof of this principle, we focused on microphthalmia-associated transcription factor a (mitfa), a dark-induced TF controlling melanogenesis in melanocytes. We demonstrated experimentally that there is a circadian rhythm of melanin synthesis mediated by mitfa. The circadian rhythm of mitfa is in turn driven by both endogenous clock and external light/dark cycle. The circadian rhythm of melanin synthesis may play an important role in zebrafish’s adaptation to daily cycle of lighting condition in the environment.
2012-04-26 | GSE37332 | GEO
Project description:Regulatory T cells (Treg cells) are important to maintain self-tolerance. In tissues, Treg cells can perform non-classical functions, for example, they are implicated in regulating metabolic processes in the adipose tissue. Their function in the liver is less well understood. We found here that Treg cells are important to secure the peripheral hepatic circadian rhythm of core-clock regulators and clock-controlled genes. Undisturbed metabolism in the liver required the presence of Treg cells and was especially important in the early postnatal phase, a distinct time period at around day 10, when the liver had not fully matured and Treg cells proliferated and accumulated in the liver-tissue. Our findings highlight a critical role for Treg cells to establish and maintain liver homeostasis.
2018-08-29 | PXD005047 | Pride
Project description:Circadian clocks are the time-keeping cellular apparatuses that are photoentrained according to the day-night photocycles on Earth 1,2. Cryptochromes (CRYs) are photoreceptors mediating photoentrainment of the circadian clock in plants and animals but how CRYs mediate light regulation of the molecular clock remains unclear 1,3. Here we show that CRYs mediate photoresponses of the circadian clock by regulating the activity of N6-methyladenosine (m6A) RNA methyltransferase and photoresponses of the epitranscriptome. In contrast to the presently known CRY complexome, the CRY2-methyltransferase complex exbibits multivalent interactions and photoresponsive condensation in response to blue light. We show that photoexcited CRY2 undergoes phosphorylation-assisted demixing to form photobodies with the properties of condensed liquid phase, which facilitates assembly of the CRY2-methyltransferase complex in the condensed liquid phase of CRY2 in vivo. The mta mutant impaired in m6A methyltransferase and the cry1cry2 mutant missing CRY photoreceptors share common defects of lengthened circadian period, reduced m6A RNA methylation, and accelerated degradation of mRNAs encoding core components of the molecular clock. These results argue for a photoentrainment mechanism by which blue light elicits liquid-liquid phase separation of the CRY2-methyltransferase complex to regulate m6A mRNA methylation, consequently suppressing mRNA degradation and period lengthening of the circadian clock
2021-07-12 | GSE152465 | GEO