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Series GSE43073 Query DataSets for GSE43073
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
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.
 
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.
 
Contributor(s) Young ME, Bray MS, Brewer RA, Pat BM, Ratcliffe WF, Garcia RA, Grenett MH, Birky TL, Peden BW, Ammons B
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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
Phone 205-975-7651
Fax 205-934-8665
Organization name University of Alabama at Birmingham
Department Genetics
Street address 1720 2nd Avenue N, RPHB 230H
City Birmingham
State/province AL
ZIP/Postal code 35294
Country USA
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (64)
GSM1055904 WT- zt6 [1]
GSM1055905 KO- zt6 [2]
GSM1055906 KO- zt0 [6]
Relations
BioProject PRJNA184344

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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
Raw data are available on Series record
Processed data included within Sample table

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