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First published online December 14, 2007
Journal of Experimental Biology 211, 15-23 (2008)
Published by The Company of Biologists 2008
doi: 10.1242/jeb.012435

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The Drosophila muscle LIM protein, Mlp84B, is essential for cardiac function

Annabelle Mery¹, Ouarda Taghli-Lamallem¹, Kathleen A. Clark², Mary C. Beckerle², Xiushan Wu³, Karen Ocorr¹ and Rolf Bodmer^1,*

¹ Development and Aging Program, Neuroscience, Aging and Stem Cell Research Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
² Hunstman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
³ Center for Heart Development, College of Life Science, Hunan Normal University, Changsha 410081, Hunan Province, People's Republic of China

^* Author for correspondence (e-mail: rolf{at}burnham.org)

Accepted 16 October 2007

Muscle LIM protein (MLP) is a cytoskeletal protein located at the Z-disc of sarcomeres. Mutations in the human MLP gene are associated with hypertrophic and dilated cardiomyopathy. MLP has been proposed to be a key player in the stretch-sensing response, but the molecular mechanisms underlying its function in normal and diseased cardiac muscle have not been established. A Drosophila homolog, Mlp84B, displays a similar subcellular localization at the Z-disc of sarcomeres throughout development and in the adult, suggesting Drosophila as a model to study MLP function. Here we employed genetic ablation and cardiac-specific RNA interference (RNAi) knockdown of mlp84B to investigate its role in heart function. We found that Mlp84B-deficient or heart-specific RNAi knockdown flies exhibit diastolic interval prolongation, heart rhythm abnormalities and a reduced lifespan, while showing no obvious structural phenotype. Our data demonstrate that Mlp84B is essential for normal cardiac function and establish the Drosophila model for the investigation of the mechanisms connecting defective cardiac Z-disc components to the development of cardiomyopathy.

Key words: Drosophila, muscle LIM protein, cardiomyopathy, cardiac function, arrhythmia, cytoskeleton, sarcomere