Project name: Rattus norvegicus

Description: The intercalated disc of cardiac myocytes is emerging as a crucial structure in the heart. Loss of intercalated disc proteins like N-cadherin causes lethal cardiac abnormalities, mutations in intercalated disc proteins cause human cardiomyopathy. A comprehensive screen for novel mechanisms in failing hearts demonstrated that expression of the lysosomal integral membrane protein-2 (LIMP-2) is increased in cardiac hypertrophy and heart failure in both rat and human myocardium. Complete loss of LIMP-2 in genetically engineered mice did not affect cardiac development; however these LIMP-2 null mice failed to mount a hypertrophic response to increased blood pressure but developed cardiomyopathy. Disturbed cadherin localization in these hearts suggested that LIMP-2 has important functions outside lysosomes. Indeed, we also find LIMP-2 in the intercalated disc, where it associates with cadherin. RNAi-mediated knockdown of LIMP-2 decreases the binding of phosphorylated b-catenin to cadherin, while overexpression of LIMP-2 has the opposite effect. Taken together, our data show that lysosomal integrated membrane protein-2 is crucial to mount the adaptive hypertrophic response to cardiac loading. We demonstrate a novel role for LIMP-2 as an important mediator of the intercalated disc.Keywords: heart failure, comparisonOverall design: overall design:3 groups of rats, 1 sample per rat:- compensated = Ren2 rat, hypertensive, no heart failure (N=6)- failure = Ren2 rat, hypertensive, no heart failure (N=4)- SD = control group, non-hypertensive (N=4)

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Release date: 2007-10-05

Last updated: 2006-02-21