title: Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy.
abstract: Drosophila is a useful model organism in which the genetics of human diseases, including recent advances in identification of the genetics of heart development and disease in the fly, can be studied. To identify novel genes that cause cardiomyopathy, we performed a deficiency screen in adult Drosophila. Using optical coherence tomography to phenotype cardiac function in awake adult Drosophila, we identified Df(1)Exel6240 as having cardiomyopathy. Using a number of strategies including customized smaller deletions, screening of mutant alleles, and transgenic rescue, we identified CG3226 as the causative gene for this deficiency. CG3226 is an uncharacterized gene in Drosophila possessing homology to the mammalian Siah-interacting protein (SIP) gene. Mammalian SIP functions as an adaptor protein involved in one of the β-catenin degradation complexes. To investigate the effects of altering β-catenin/Armadillo signaling in the adult fly, we measured heart function in flies expressing either constitutively active Armadillo or transgenic constructs that block Armadillo signaling, specifically in the heart. While, increasing Armadillo signaling in the heart did not have an effect on adult heart function, decreasing Armadillo signaling in the fly heart caused the significant reduction in heart chamber size. In summary, we show that deletion of CG3226, which has homology to mammalian SIP, causes cardiomyopathy in adult Drosophila. Alterations in Armadillo signaling during development lead to important changes in the size and function of the adult heart.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Casad
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Daniels
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Wolf
authors.forename: Howard A
authors.initials: HA
authors.lastname: Rockman
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics*; D004195:Disease Models, Animal; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C410595:poly-U binding splicing factor 60KDa