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Leucine-rich repeat containing 10 (LRRC10) is a cardiac-specific protein exclusively expressed in embryonic and adult cardiomyocytes. However, the role of LRRC10 in mammalian cardiac physiology remains unknown. To determine if LRRC10 is critical for cardiac function, Lrrc10-null (Lrrc10(-/-)) mice were analyzed. Lrrc10(-) (/-) mice exhibit prenatal systolic dysfunction and dilated cardiomyopathy in postnatal life. Importantly, Lrrc10(-/-) mice have diminished cardiac performance in utero, prior to ventricular dilation observed in young adults. We demonstrate that LRRC10 endogenously interacts with α-actinin and α-actin in the heart and all actin isoforms in vitro. Gene expression profiling of embryonic Lrrc10(-/-) hearts identified pathways and transcripts involved in regulation of the actin cytoskeleton to be significantly upregulated, implicating dysregulation of the actin cytoskeleton as an early defective molecular signal in the absence of LRRC10. In contrast, microarray analyses of adult Lrrc10(-/-) hearts identified upregulation of oxidative phosphorylation and cardiac muscle contraction pathways during the progression of dilated cardiomyopathy. Analyses of hypertrophic signal transduction pathways indicate increased active forms of Akt and PKCε in adult Lrrc10(-/-) hearts. Taken together, our data demonstrate that LRRC10 is essential for proper mammalian cardiac function. We identify Lrrc10 as a novel dilated cardiomyopathy candidate gene and the Lrrc10(-/-) mouse model as a unique system to investigate pediatric cardiomyopathy.
Pubmed ID: 23236519
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The American Heart Association (AHA) publishes medical scientific statements on various cardiovascular disease and stroke topics. AHA volunteer scientists and healthcare professionals write the papers. The statements are supported by scientific studies published in recognized journals and have a rigorous review and approval process. Scientific statements generally include a review of data available on a specific subject, an evaluation on its relationship to overall cardiovascular disease science, and often an American Heart Association position on the basis of that evaluation. The American Heart Association sponsors accredited scientific conferences and professional development seminars to disseminate new and emerging scientific knowledge and stimulate discussion on future research and the application of knowledge. Keywords: Heart, Cardiovascular, Disease, Stroke, Volunteer, Scientist, Healthcare, Development, Knowledge,
View all literature mentionsIntegrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
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View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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