Allele Dmel\unc-45^{dsRNA.Scer\UAS.cUa}

General Information
Symbol	Dmel\unc-45^{dsRNA.Scer\UAS.cUa}	Species	D. melanogaster
Name		FlyBase ID	FBal0269876
Feature type	allele	Associated gene	Dmel\unc-45

Allele class
Mutagen	in vitro construct - RNAi, in vitro construct - regulatory fusion
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Nature of the Allele
Allele class
Mutagen	in vitro construct - regulatory fusion (Melkani et al., 2011) in vitro construct - RNAi (Melkani et al., 2011)
Mutations Mapped to the Genome

Type Location Additional Notes References
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name

UniProtKB/Swiss-Prot
UniProtKB/TrEMBL

Progenitor genotype
Nature of the lesion	Statement Reference Scer\UAS regulatory sequences drive expression of an RNAi construct targeting unc-45. (Melkani et al., 2011)
Carried in construct	P{UAS-unc-45.RNAi.U} (Melkani et al., 2011)
Cytology
Phenotypic Data
Phenotypic Class
	lethal, with Scer\GAL4^how-24B (Melkani et al., 2011) short lived, with Scer\GAL4^HCH.Hand (Melkani et al., 2011)
Phenotype Manifest In
	adult heart, with Scer\GAL4^HCH.Hand (Melkani et al., 2011) adult heart, with Scer\GAL4^tin.CΔ4, Scer\GAL80^ts.αTub84B (Melkani et al., 2011) adult heart chamber 1, with Scer\GAL4^HCH.Hand (Melkani et al., 2011) adult heart chamber 2, with Scer\GAL4^HCH.Hand (Melkani et al., 2011) embryonic/larval heart \| P-stage, with Scer\GAL4^HCH.Hand (Melkani et al., 2011) embryonic/larval heart \| third instar larval stage, with Scer\GAL4^HCH.Hand (Melkani et al., 2011) myofibril, with Scer\GAL4^HCH.Hand (Melkani et al., 2011)
Detailed Description
	Statement Reference 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]. (Melkani et al., 2011)
External Data
Linkouts
Interactions
Phenotypic Class
Phenotype Manifest In
Additional Comments
Genetic Interactions
Statement Reference
Xenogenetic Interactions
Statement Reference
Complementation & Rescue Data
Comments
Stocks ( 0 )

Notes on Origin
Discoverer

External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 1 )
Reported As
Symbol Synonym	unc-45^{dsRNA.Scer\UAS.cUa}
Name Synonym
Secondary FlyBase IDs

References ( 1 )
Research paper	Melkani et al., 2011, PLoS ONE 6(7): e22579 The UNC-45 Chaperone Is Critical for Establishing Myosin-Based Myofibrillar Organization and Cardiac Contractility in the Drosophila Heart Model. [FBrf0214543]

Allele Dmel\unc-45dsRNA.Scer\UAS.cUa

Allele Dmel\unc-45^{dsRNA.Scer\UAS.cUa}