Open AccessDystrophin deficiency in Drosophila reduces lifespan and causes a dilated cardiomyopathy phenotype
Author(s) -
TaghliLamallem Ouarda,
Akasaka Takeshi,
Hogg Grant,
Nudel Uri,
Yaffe David,
Chamberlain Jeffrey S.,
Ocorr Karen,
Bodmer Rolf
Publication year - 2008
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2008.00367.x
Subject(s) - dilated cardiomyopathy , biology , dystrophin , cardiomyopathy , gene knockdown , phenotype , gene isoform , muscular dystrophy , cardiac function curve , genetics , medicine , endocrinology , gene , heart failure
Summary A number of studies have been conducted recently on the model organism Drosophila to determine the function of genes involved in human disease, including those implicated in neurological disorders, cancer and metabolic and cardiovascular diseases. The simple structure and physiology of the Drosophila heart tube together with the available genetics provide a suitable in vivo assay system for studying cardiac gene functions. In our study, we focus on analysis of the role of dystrophin (Dys) in heart physiology. As in humans, the Drosophila dys gene encodes multiple isoforms, of which the large isoforms ( DLPs ) and a truncated form ( Dp117 ) are expressed in the adult heart. Here, we show that the loss of dys function in the heart leads to an age‐dependent disruption of the myofibrillar organization within the myocardium as well as to alterations in cardiac performance. dys RNAi‐mediated knockdown in the mesoderm also shortens lifespan. Knockdown of all or deletion of the large isoforms increases the heart rate by shortening the diastolic intervals (relaxation phase) of the cardiac cycle. Morphologically, loss of the large DLPs isoforms causes a widening of the cardiac tube and a lower fractional shortening, a phenotype reminiscent of dilated cardiomyopathy. The dilated dys mutant phenotype was reversed by expressing a truncated mammalian form of dys ( Dp116 ). Our results illustrate the utility of Drosophila as a model system to study dilated cardiomyopathy and other muscular‐dystrophy‐associated phenotypes.