Document Detail


Galactokinase Is a Novel Modifier of Calcineurin-Induced Cardiomyopathy in Drosophila.
MedLine Citation:
PMID:  25081566     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Activated/uninhibited calcineurin is both necessary and sufficient to induce cardiac hypertrophy, a condition that often leads to dilated cardiomyopathy, heart failure, and sudden cardiac death. We expressed constitutively active calcineurin in the adult heart of Drosophila melanogaster and identified enlarged cardiac chamber dimensions and reduced cardiac contractility. In addition, expressing constitutively active calcineurin in the fly heart using the Gal4/UAS system induced an increase in heart wall thickness. We performed a targeted genetic screen for modifiers of calcineurin-induced cardiac enlargement based on previous calcineurin studies in the fly and identified galactokinase as a novel modifier of calcineurin-induced cardiomyopathy. Genomic deficiencies spanning the galactokinase locus, transposable elements that disrupt galactokinase, and cardiac-specific RNAi knockdown of galactokinase suppressed constitutively active calcineurin-induced cardiomyopathy. In addition, in flies expressing constitutively active calcineurin using the Gal4/UAS system, a transposable element in galactokinase suppressed the increase in heart wall thickness. Lastly, genetic disruption of galactokinase suppressed calcineurin-induced wing vein abnormalities. Collectively, we generated a model for discovering novel modifiers of calcineurin-induced cardiac enlargement in the fly and identified galactokinase as a previously unknown regulator of calcineurin-induced cardiomyopathy in adult Drosophila.
Authors:
Teresa E Lee; Lin Yu; Matthew J Wolf; Howard A Rockman
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-31
Journal Detail:
Title:  Genetics     Volume:  -     ISSN:  1943-2631     ISO Abbreviation:  Genetics     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-8-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374636     Medline TA:  Genetics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, The Genetics Society of America.
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