A Database of Drosophila Genes & Genomes

FB2013_03, released May 7th, 2013
 

Allele Zzzz\CAGrCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG

General Information
SymbolZzzz\CAGrCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAGSpeciesa. artificial
NameFlyBase IDFBal0277239
Feature typealleleAssociated geneZzzz\CAG
Allele class
Mutagenin vitro construct - regulatory fusion
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Description
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FB2013_03
FB2013_02
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Allele class
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Protein sequence
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Nature of the lesion
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Scer\UAS regulatory sequences drive expression of an approximately 100 nt CAG repeat in reverse orientation.
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Cytology
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At the standard culture temperature of 25[o]C, a significant reduction in viability is observed for one of two independent Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG]-expressing lines using Scer\GAL4[da.G32] compared with empty vector controls. When grown at 29[o]C, complete lethality is observed in Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG]-expressing progeny but not in empty vector controls using Scer\GAL4[da.G32]. Closer physical examination of adult flies reveals a phenotype in viable progeny expressing Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] using Scer\GAL4[da.G32] at 25[o]C whereby the tergites of the dorsal abdomen are not correctly formed. In wild-type adults, the abdomen contains a series of regularly arranged tergites, while in Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG]-expressing flies one or more of the tergite bands is split down the midline so that the two sides do not meet at all, or meet only partially. Expression of Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] in histoblasts using Scer\GAL4[T155] does not result in significant tergite abnormalities.
Flies expressing Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] alone under the control of Scer\GAL4[elav-C155] display normal eye patterning. Co-expression of Zzzz\CAG[99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] and Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] under the control of Scer\GAL4[GMR.PF] results in a rough eye phenotype. Pan-neural co-expression of Zzzz\CAG[99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] and Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] using Scer\GAL4[elav-C155] results in a significant level of male lethality, while females show a mild phenotype in the adult eye.
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Statistical analysis reveals a significant decrease in the proportion of flies expressing Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] using Scer\GAL4[da.G32] that show any phenotype in the presence of heterozygous mbl[E27] compared with flies expressing Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] alone. However, no change is observed when comparing the proportion within the strongest two categories only, perhaps indicating that only those with the weakest phenotype are suppressed. Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] expression using Scer\GAL4[da.G32] in the presence of heterozygous Dcr-2[L811fsX] does not give significantly different phenotype severity compared to Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] expression in a wild-type Dcr-2 background. In one of two lines expressing Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] using Scer\GAL4[da.G32] in the presence of heterozygous Dcr-1[Q1147X] the proportion of progeny with any tergite-disruption phenotype, and those with a strong phenotype, is significantly reduced compared with flies expressing Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] alone.
Heterozygous Dcr-2[L811fsX] suppresses the eye-phenotype resulting from the co-expression of Zzzz\CAG[99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] and Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] under the control of Scer\GAL4[GMR.PF]. In addition, the overall disruption observed in patterning of the internal structure of the eye is significantly reduced in the presence of heterozygous Dcr-2[L811fsX] as revealed by sections through adult eyes. Co-expression of Dcr-2[Scer\UAS.cDa] with Zzzz\CAG[99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG]/Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] at 18[o]C results in a loss-of-pigment phenotype which is not observed when Zzzz\CAG[99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG]/Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] is expressed under the control of Scer\GAL4[GMR.PF]. The normal eye phenotype of flies expressing Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] under the control of Scer\GAL4[GMR.PF] is not modified by the co-expression of Dcr-2[Scer\UAS.cDa]. The eye phenotype resulting from the co-expression of Zzzz\CAG[99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] and Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] using Scer\GAL4[elav-C155] is significantly enhanced when Dcr-2[Scer\UAS.cDa] is also co-expressed. Co-expression of Zzzz\CAG[99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] and Zzzz\CAG[rCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG] under the control of Scer\GAL4[elav.PLu] fails to induce defects in the adult eye or viability, however, flies show an age-dependent movement disorder (failure-to-climb phenotype) compared with controls.
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Reported As
Symbol Synonym
Zzzz\CAGrCUG.99.Scer\UAS.T:Hsap\MYC,T:Zzzz\FLAG
 
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Research paper
Lawlor et al., 2012, PLoS ONE 7(6): e38516
Ubiquitous Expression of CUG or CAG Trinucleotide Repeat RNA Causes Common Morphological Defects in a Drosophila Model of RNA-Mediated Pathology. [FBrf0218612]
Lawlor et al., 2011, Hum. Mol. Genet. 20(19): 3757--3768
Double-stranded RNA is pathogenic in Drosophila models of expanded repeat neurodegenerative diseases. [FBrf0215240]