|Feature type||allele||Associated gene||Dmel\unc-45|
|Mutagen||in vitro construct - RNAi, in vitro construct - regulatory fusion|
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|Nature of the Allele|
|Mutations Mapped to the Genome|
|Associated Sequence Data|
|Nature of the lesion|
|Carried in construct|
|Phenotype Manifest In|
Analysis of heart function in flies expressing unc-45[dsRNA.Scer\UAS.cUa] under the control of Scer\GAL4[HCH.Hand] reveals severe heart defects compared with controls. Hearts with cardiac unc-45[dsRNA.Scer\UAS.cUa]-expression are significantly dilated in both the conical chamber and the third abdominal segment heart and exhibit dramatically arrhythmic beating patterns, compared with aged-matched control hearts. Severe cardiac dysfunction is observed as early as late pupal stages. In contrast, no major apparent cardiac defects are observed in hearts of third instar larvae and young (white) pupae expressing unc-45[dsRNA.Scer\UAS.cUa] via Scer\GAL4[HCH.Hand] regarding cardiac contractility compared to wild-type. However, quantitative analyses of cardiac data obtained from both third instar larvae and young pupae reveal that the unc-45[dsRNA.Scer\UAS.cUa]-expressing hearts show a small but significant increase in heart rate (tachycardia) compared with age-matched control. In addition to tachycardia, expression of unc-45[dsRNA.Scer\UAS.cUa] in third instar larval hears results in mild but significant cardiac dilation, which is more evident after metamorphosis. Both diastolic and systolic diameters of unc-45[dsRNA.Scer\UAS.cUa]-expressing third instar larval hearts are significantly larger than control hearts. Although unc-45[dsRNA.Scer\UAS.cUa]-expressing third instar larval hearts show tachycardia, their cardiac performance is depressed compared with control third instar larvae. Conditional expression of unc-45[dsRNA.Scer\UAS.cUa] under the control of both Scer\GAL4[tin.CΔ4] and Scer\GAL80[ts.αTub84B] results in a severe cardiac phenotype in adult hearts throughout life. For example, one week old hearts conditionally expressing unc-45[dsRNA.Scer\UAS.cUa] beginning before metamorphosis (third instar larval stage) show prolonged systolic and diastolic intervals compared with controls. In addition, such unc-45[dsRNA.Scer\UAS.cUa]-expressing hearts are dilated, their fractional shortening is reduced, and cardiac arrhythmias are increased. Severe cardiac defects are also apparent in newly enclosed adults and late pupae when unc-45[dsRNA.Scer\UAS.cUa] expression is induced at the beginning of the pupal stage instead of the third instar larval stage. In contrast to the above date, when unc-45[dsRNA.Scer\UAS.cUa] is expressed in the heart after metamorphosis (adult flies), dilation of the heart does not occur, however, systolic and diastolic intervals are prolonged and arrhythmias are elevated. Similar results are obtained when examining the hearts of older flies. Quantitative analysis of various cardiac physiological parameters in 1-3 week old fly hearts expressing unc-45[dsRNA.Scer\UAS.cUa] via Scer\GAL4[HCH.Hand] reveals a significant prolongation of the heartbeat length, compared with wild-type, that manifests in an increase of both systolic and diastolic intervals. Particularly dramatic is the cardiac dilation due to both systolic and diastolic heart diameter increases in unc-45[dsRNA.Scer\UAS.cUa]-expressing hearts compared with control hearts. The observed extreme cardiac dilation is accompanied by a significant reduction in heart contractility, which is quantified in a decreased fractional shortening. The incidence of arrhythmias is also much higher in unc-45[dsRNA.Scer\UAS.cUa]-expressing hearts than that in controls. This is in large part due to the frequent occurrence of asystolies, intermittent stoppages in heartbeat. Cardiac expression of unc-45[dsRNA.Scer\UAS.cUa] under the control of Scer\GAL4[HCH.Hand] has a drastic negative impact on the life-span of flies. Mesodermal expression of unc-45[dsRNA.Scer\UAS.cUa] under the control of Scer\GAL4[how-24B] results in early developmental lethality. Myofibrillar disorganization is apparent in hearts expressing unc-45[dsRNA.Scer\UAS.cUa] under the control of Scer\GAL4[HCH.Hand] compared with wild-type hearts. unc-45[+t] significantly improves the cardiac phenotypes and life-span defects resulting from the expression of unc-45[dsRNA.Scer\UAS.cUa] under the control of Scer\GAL4[HCH.Hand].
|Phenotype Manifest In|
|Complementation & Rescue Data|
|Stocks ( 0 )|
|Notes on Origin|
|External Crossreferences & Linkouts|
|Synonyms & Secondary IDs ( 1 )|
|Secondary FlyBase IDs|
|References ( 1 )|