Serial examination of an inducible and reversible dilated cardiomyopathy in individual adult Drosophila.
Recent work has demonstrated that Drosophila can be used as a model of dilated cardiomyopathy, defined as an enlarged cardiac chamber at end-diastole when the heart is fully relaxed and having an impaired systolic function when the heart is fully contracted. Gene mutations that cause cardiac dysfunction in adult Drosophila can result from abnormalities in cardiac development or alterations in post-developmental heart function. To clarify the contribution of transgene expression to post-developmental cardiac abnormalities, we applied strategies to examine the temporal and spacial effects of transgene expression on cardiac function. We engineered transgenic Drosophila based on the well-characterized temperature-sensitive Gal80 protein in the context of the bipartite Gal4/UAS transgenic expression system in Drosophila employing the cardiac specific driver, tinCDelta4-Gal4. Then, we developed a strategy using optical coherence tomography to serially measure cardiac function in the individual flies over time course of several days. As a proof of concept we examined the effects of the expression of a human mutant delta-sarcoglycan associated with familial heart failure and observed a reversible, post-developmental dilated cardiomyopathy in Drosophila. Our results show that the unique imaging strategy based on the non-destructive, non-invasive properties of optical coherence tomography can be applied to serially examine cardiac function in individual adult flies. Furthermore, the induction and reversal of cardiac transgene expression can be investigated in adult flies thereby providing insight into the post-developmental effects of transgene expression.
Kim
Il-Man
IM
Department of Medicine, Duke University, Durham, North Carolina, USA.
Wolf
Matthew J
MJ
D000818:Animals; D030801:Animals, Genetically Modified; D009202:Cardiomyopathies; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013696:Temperature; D019076:Transgenes
D029721:Drosophila Proteins