Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure

Chen, J. F., Murchison, E. P., Tang, R., Callis, T. E., Tatsuguchi, M., Deng, Z., Rojas, M., Hammond, S. M., Schneider, M. D., Selzman, C. H., Meissner, G., Patterson, C., Hannon, G. J., Wang, D. Z. (February 2008) Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. Proc Natl Acad Sci U S A, 105 (6). pp. 2111-2116. ISSN 0027-8424

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URL: http://www.ncbi.nlm.nih.gov/pubmed/18256189
DOI: 10.1073/pnas.0710228105

Abstract

Cardiovascular disease is the leading cause of human morbidity and mortality. Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy associated with heart failure. Here, we report that cardiac-specific knockout of Dicer, a gene encoding a RNase III endonuclease essential for microRNA (miRNA) processing, leads to rapidly progressive DCM, heart failure, and postnatal lethality. Dicer mutant mice show misexpression of cardiac contractile proteins and profound sarcomere disarray. Functional analyses indicate significantly reduced heart rates and decreased fractional shortening of Dicer mutant hearts. Consistent with the role of Dicer in animal hearts, Dicer expression was decreased in end-stage human DCM and failing hearts and, most importantly, a significant increase of Dicer expression was observed in those hearts after left ventricle assist devices were inserted to improve cardiac function. Together, our studies demonstrate essential roles for Dicer in cardiac contraction and indicate that miRNAs play critical roles in normal cardiac function and under pathological conditions.

Item Type: Paper
Uncontrolled Keywords: cardiac function microRNA MUSCLE-SPECIFIC MICRORNA CARDIAC-HYPERTROPHY MUTATIONS CARDIOGENESIS EXPRESSION RELEASE CELLS ALTER MICE
Subjects: diseases & disorders > cardiovascular diseases
bioinformatics > genomics and proteomics > analysis and processing > DNA RNA Processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA expression
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organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
CSHL Authors:
Communities: CSHL labs > Hannon lab
Watson School > Publications
Depositing User: Tom Adams
Date: February 2008
Date Deposited: 13 Jul 2011 20:37
Last Modified: 22 Sep 2014 15:53
PMCID: PMC2542870
Related URLs:
URI: http://repository.cshl.edu/id/eprint/7703

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