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Series GSE40677 Query DataSets for GSE40677
Status Public on Aug 26, 2013
Title Gene expression analysis in mice with heart muscle-specific repression of CELF activity (MHC-CELFdelta)
Organism Mus musculus
Experiment type Expression profiling by array
Summary Members of the CUG-BP, Elav-like family (CELF) regulate alternative splicing in the heart. In MHC-CELFdelta transgenic mice, CELF splicing activity is inhibited postnatally in heart muscle via expression of a nuclear dominant negative CELF protein under an a-myosin heavy chain promoter. MHC-CELFdelta mice develop dilated cardiomyopathy characterized by alternative splicing defects, enlarged hearts, and severe contractile dysfunction. In this study, gene expression profiles in the hearts of wild type, high- and low-expressing lines of MHC-CELFdelta mice were compared using microarrays. Gene ontology and pathway analyses identified contraction and calcium signaling as the most affected processes. Network analysis revealed that the serum response factor (SRF) network is highly affected. Downstream targets of SRF were up-regulated in MHC-CELFdelta mice compared to the wild type, suggesting an increase in SRF activity. Although SRF levels remained unchanged, known inhibitors of SRF activity were down-regulated. These results suggest a role for CELF-mediated alternative splicing in the regulation of contractile gene expression, achieved in part through modulating the activity of SRF, a key cardiac transcription factor.
 
Overall design Microarray analysis was performed on total RNA extracted from whole hearts of three MHC-CELFdelta-10 and three MHC-CELFdelta-574 females collected at weaning (three weeks old). Three female wild type littermates from each line were used as controls (n = 6 wild type in total).
 
Contributor(s) Dasgupta T, Stillwagon SJ, Ladd AN
Citation(s) 23437181
Submission date Sep 07, 2012
Last update date Jan 16, 2019
Contact name Andrea Ladd
E-mail(s) ladda@ccf.org
Organization name Cleveland Clinic Lerner Research Institute
Department Cell Biology
Street address 9500 Euclid Avenue
City Cleveland
State/province OH
ZIP/Postal code 44195
Country USA
 
Platforms (1)
GPL6887 Illumina MouseWG-6 v2.0 expression beadchip
Samples (12)
GSM994767 Heart_3wks_female_wildtype_sevline_rep1
GSM994768 Heart_3wks_female_wildtype_sevline_rep2
GSM994769 Heart_3wks_female_wildtype_sevline_rep3
Relations
BioProject PRJNA174626

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
GSE40677_RAW.tar 19.5 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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