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Status |
Public on Jan 01, 2014 |
Title |
IMPACT OF CARDIOMYOCYTE-SPECIFIC BMAL1 DELETION ON MYOCARDIAL GENE EXPRESSION, METABOLISM, AND CONTRACTILE FUNCTION |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Circadian clocks are cell autonomous, transcriptionally-based, molecular mechanisms that confer the selective advantage of anticipation, enabling cells/organs to respond to environmental factors in a temporally appropriate manner. Critical to circadian clock function are two transcription factors, CLOCK and BMAL1. Previous studies in our laboratory have highlighted roles for CLOCK in cardiac physiology/pathophysiology. Here, we describe transcriptional, metabolic, and functional consequences of cardiomyocyte-specific Bmal1 knockout (CBK). Microarray analysis revealed 2037 differentially expressed genes in CBK hearts, many of which were previously identified in cardiomyocyte-specific Clock mutant (CCM) hearts. Subsequent analysis showed that Beta-hydroxybutyrate dehydrogenase 1 mRNA, protein, and enzymatic activity are markedly depressed in both CBK and CCM hearts, as is myocardial Beta-hydroxybutyrate oxidation, revealing a novel role for the circadian clock in ketone body utilization. A number of genes encoding for collagen isoforms were identified as oscillating in a time-of-day-dependent manner in wild-type, but not CBK, hearts, including col3a1, col4a1, and col4a2. Chronic induction of collagen isoform genes in CBK hearts was associated with severe age-dependent depression of cardiac function. Development of cardiomyopathy in CBK mice was associated with early mortality; all CBK mice die by one year of age. These studies highlight novel critical functions for BMAL1 in the heart, including regulation of ketone body metabolism and the extracellular matrix.
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Overall design |
RNA from whole hearts collected every 3 hours for 24 hours from wildtype and CBK mice was isolated and analyzed using MouseRef-8_V2 BeadChips (Illumina, Inc.). The 24-hour data were examined for rhythmicity using cosinor analysis and differences in rhythmicity between genotype groups were further examined for differences in the model fitting parameters.
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Contributor(s) |
Young ME, Bray MS, Brewer RA, Pat BM, Ratcliffe WF, Garcia RA, Grenett MH, Birky TL, Peden BW, Ammons B |
Citation missing |
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Submission date |
Dec 20, 2012 |
Last update date |
Jun 14, 2018 |
Contact name |
Molly Bray |
E-mail(s) |
mbray@uab.edu
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Phone |
205-975-7651
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Fax |
205-934-8665
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Organization name |
University of Alabama at Birmingham
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Department |
Genetics
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Street address |
1720 2nd Avenue N, RPHB 230H
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City |
Birmingham |
State/province |
AL |
ZIP/Postal code |
35294 |
Country |
USA |
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Platforms (1) |
GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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Samples (64)
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Relations |
BioProject |
PRJNA184344 |
Supplementary file |
Size |
Download |
File type/resource |
GSE43073_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
GSE43073_non-normalized.txt.gz |
9.6 Mb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
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