|
| 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 |
| GSM994770 |
Heart_3wks_female_transgenic_sevline_rep1 |
| GSM994771 |
Heart_3wks_female_transgenic_sevline_rep2 |
| GSM994772 |
Heart_3wks_female_transgenic_sevline_rep3 |
| GSM994773 |
Heart_3wks_female_wildtype_mildline_rep1 |
| GSM994774 |
Heart_3wks_female_wildtype_mildline_rep2 |
| GSM994775 |
Heart_3wks_female_wildtype_mildline_rep3 |
| GSM994776 |
Heart_3wks_female_transgenic_mildline_rep1 |
| GSM994777 |
Heart_3wks_female_transgenic_mildline_rep2 |
| GSM994778 |
Heart_3wks_female_transgenic_mildline_rep3 |
|
| Relations |
| BioProject |
PRJNA174626 |
Less...
More...