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General Information
Symbol
Hsap\ATXN3tr.Q78.UAS.Tag:HA
Species
H. sapiens
Name
FlyBase ID
FBal0090630
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
UAS-MJDtr-Q78, UAS-SCA3trQ78, UAS-SCA3tr-Q78, MJDtr-Q78, SCA3trQ78, UAS-MJDtr-Q78(S), SCA3tr-Q78, UAS-MJDtrQ78, UAS-MJD-78Q, UAS-SCA3trQ78(S)
Allele class
Nature of the Allele
Allele class
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Carried in construct
Cytology
Nature of the lesion
Statement
Reference
A truncated form of Hsap\ATXN3, consisting of an expanded length glutamine tract (78 repeats) flanked upstream by 12 amino acids and downstream by the carboxy terminal 43 amino acids of Hsap\ATXN3, is expressed under the control of UASt regulatory sequences. The Hsap\ATXN3 protein is tagged at the N-terminal end with Tag:HA.
Allele components
Product class / Tool use(s)
Encoded product / tool
Expression Data
Reporter Expression
Additional Information
Statement
Reference
 
Marker for
Reflects expression of
Reporter construct used in assay
Human Disease Associations
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 1 )
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
is ameliorated by Rac1UAS.cLa
is exacerbated by Rac1V12.UAS
is exacerbated by CG7130GD2776
is exacerbated by Atg7GD11671
is exacerbated by Atg12JF02704
is exacerbated by Atg8aHMS01328
is ameliorated by CG9934JF02691
is ameliorated by DnaJ-1UAS.cKa
is ameliorated by effHM05268
is exacerbated by sip3GD3145
is ameliorated by parkHMS01651
is exacerbated by STUB1HMS00986
is ameliorated by embE2-1A
is ameliorated by dbrEP9
is ameliorated by dbrEP456
is ameliorated by orb2B8-S
is ameliorated by Faf2E659
is ameliorated by wechE546
is ameliorated by mrjE1050
is exacerbated by Cdk5GD13840
is ameliorated by embEY08770
is exacerbated by embJF01311
is ameliorated by cdmGS17666
is NOT exacerbated by cdmJF01428
is exacerbated by UckGD229
is exacerbated by TbpsI10
is exacerbated by TbpUAS.cHa
is ameliorated by nejEP1410
is exacerbated by Khc9
is exacerbated by loqsf00791
is ameliorated by mir-banB90.1
is exacerbated by U2af50XR15
is exacerbated by mblUAS.cLa
is ameliorated by Rpn11DANC
Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
 
The expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in flies results in late-onset, progressive, neurodegenerative phenotypes, with similar features to SCA3/MJD patients.
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference
Adults expressing Hsap\ATXN3tr.Q78.UAS.Tag:HA under the control of Scer\GAL4GMR.PU display progressive eye defects, including loss of pigmentation.
The expression of Hsap\ATXN3tr.Q78.UAS.Tag:HA under the control of Scer\GAL4GMR.PF induces a rough eye phenotype, associated with depigmentation, necrotic spots, and disordered bristles; expression under the control of Scer\GAL4ninaE.PT also leads to milder, later-onset (20 days old individuals) eye defects, namely disorganized ommatidia and tissue dissociation associated with the appearance of vacuoles, as compared to controls.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU leads to age-progressive eye degeneration, manifested by loss of eye pigmentation in adult flies.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU induces a rough eye phenotype in the adult eye.
Flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU exhibit glassy and depigmented eyes with abnormal lenses, as compared to controls.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 driven by Scer\GAL4GMR.PF leads to degeneration of ommatidia in fly eyes (eyes are rough, speckled or collapsed).
Scer\GAL4GMR.PF-mediated expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 results in a rough eye.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF in larval eye imaginal discs causes a severe eye ablation phenotype.
Feeding flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav-C155 any of -(-)deprenyl (DEP), 2-amino-4,7-dimethylbenzothiazole (PGL) or hydroxynonenal (HNE) significantly decreases the number of aggregates seen in the brain.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in the retina using Scer\GAL4GMR.PU severely disrupts eye morphology,resulting in loss of pigmentation, neuron death, and retinal collapse. Ubiquitous expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 using Scer\GAL4da.PU shortens lifespan compared to wild-type. Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in the nervous system using Scer\GAL4nrv2.PS leads to decreased locomotion compared to wild-type. Cystamine treatment enhances neurodegeneration in flies expressing Scer\GAL4GMR.PU>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 driven by Scer\GAL4GMR.long results in depigmentation of the external retina and near complete loss (and detachment from the lamina) of the radial ommatidial array of the internal eye.
The expression of Hsap\ATXN3tr.Q78.UAS.Tag:HA under the control of Scer\GAL4GMR.PU leads to strong toxicity in the eye, as judged by a progressive loss of eye pigmentation.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 driven by Scer\GAL4repo.PU (along with Tub-Gal80ts) leads to neurodegeneration in 7 day old flies (presence of vacuoles).
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in the drosophila eye, under the control of Scer\GAL4GMR.long results in robust degeneration of internal and external structures in the adylt eye.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in glia under the control of Scer\GAL4repo.PU produces significant pathological changes in the adult brain, including large vacuoles, but no mitochondrial enlargement is seen.
The eyes of 7-week old flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU exhibit total depigmentation with small, scattered necrotic spots. The hexagonal arrangement of photoreceptor clustering has completely disappeared, and numerous protein aggregates are observed.
Eye-specific expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1, under the control of Scer\GAL4GMR.long results in eye degeneration.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in the developing eye, under the control of Scer\GAL4GMR.long, results in mild disruption of the regular, external lattice of the eye in adult flies. Stronger expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 results in a greater loss of cell integrity, and the pigmentation of the adult flies is completely faded with black point-like necrosis. The fly eyes undergo late-onset, progressive degeneration during adult life. Prolonged treatment with LiCl at a certain range (1-20mM) results in a dramatic improvement of eye depigmentation at 5 days after eclosion, with an obvious increase of pigmentation, decreased black point-like necrosis, and a nearly normal ommatidial pattern of the photoreceptor rhabdomeres. The most notable improvement is observed at the range of 15-20mM. Neuronal expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1, under the control of Scer\GAL4nrv2.PS, causes decreased locomotor ability and a reduction in adult life span. The addition of 0-10mM LiCl to 1 day old Scer\GAL4nrv2.PS>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 adult flies generates a dose-dependent increase in locomotor ability, compared to non-treated controls, but as the dose is gradually increased to 15mM, locomotor ability may be further impaired. The median life span of flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4nrv2.PS increases from 41-47 days to 52-62 days (depending on the strength of expression), when these flies are treated with 5-15mM LiCl. However, a dose of 20mM LiCl has no effect on median life span.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in the developing eye under the control of Scer\GAL4GMR.PF causes massive degeneration of external and internal structures. Degeneration as a result of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 expression is marked by loss of pigmentation in the external eye, loss of ommatidia, a dramatic reduction in retinal depth, and the presence of aggregated structures/inclusions.
Flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.long have a rough eye phenotype.
Larval ddaE neurons expressing Hsap\ATXN3tr.Q78.UAS.Tag:HA under the control of Scer\GAL4221 show a significant increase in growing microtubules within dendrites, as compared to neurons in controls; these neurons show a severe increase in the proportion of dendrites persisting 18h after dendrite severance, as compared to similarly injured control neurons; these neurons also show a significant increase in growing microtubules within axons and significantly delayed axon beading 12h after axotomy, as compared to similarly injured control neurons. Larval ddaC neurons expressing Hsap\ATXN3tr.Q78.UAS.Tag:HA under the control of Scer\GAL4477 show a moderately reduced dendritic arborization which does not seem to expand as the larval life progresses, as compared to controls. 12h after axotomy, these neurons show a significant increase in growing microtubules within axons, as compared to similarly injured control neurons. Expression of Hsap\ATXN3tr.Q78.UAS.Tag:HA under the control of Scer\GAL4GMR.long induces eye defects, which range from discoloration to eye collapse and necrosis, as compared to controls.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4ninaE.PT results in inclusion formation, a decrease in polyQ protein solubility and progressive neural loss. At 21 days the number of photoreceptors per ommatidium is reduced in male flies compared to controls.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4ninaE.PT results in loss of photoreceptor cells in the ommatidia.
Flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.long display a rough eye phenotype characterized by pigment loss, a disturbed external surface and appearance of necrotic spots due to degeneration of photoreceptors and other retinal cells.
Larvae expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in class IV da neurons under the control of Scer\GAL4ppk.PG exhibit striking dendritic abnormalities. Terminal dendritic branching and complexity is greatly reduced compared to controls, whereas the major dendrite branches are unaffected. At 96h after egg laying larvae almost completely blocked growth and branch initiation of terminal dendrites and the proportion of terminal dendrites showing branch retraction is similar to controls. Alterations are seen to the F-actin structures in distal dendrites, but stable microtubular structures are unaffected. The dendrite blebbing and breakages characteristic of dying da neurons is not observed. Restricting expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 to the adult stages using an RU486-inducible Scer\GAL4ppk.Switch.PR driver also causes a similar loss dendritic terminals in class IV da neurons. These dendritic defects are observed even when administration of RU486 is restricted to 3 days after eclosion, and do not appear to be reversed with aging. Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in class III da neurons under the control of Scer\GAL4109(2)80 results in reduced filopodia (dendrite terminal structures) formation compared to controls. Major dendritic structures are unaffected. Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in class I da neurons under the control of Scer\GAL4221 has no obvious effects on their dendrites. Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in dorsal cluster neurons under the control of Scer\GAL4109(2)80 results in a reduction in F-actin structures in distal dendrites. Microtubular structures are not obviously altered.
Expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 in the developing eye under the control of Scer\GAL4GMR.PF induces clear defects in the eye, with defective ommatidia seen in 18% of cases.
When Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 expression is induced 'early', only for 4 days after eclosion (using the 'TARGET' system and Scer\GAL4GMR.PF and Scer\GAL80ts.αTub84B), rhabdomere loss is not observable until 40 days of age. However, when Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 expression os induced from 20 to 24 days of age (i.e. 'late'), neurodegeneration with rhabdomere loss of the ommatidia is observable at 40 days of age, suggesting that Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 expression in older flies causes more severe neurodegeneration than expression in younger flies.
Overexpression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU results in massive degeneration of retinal cells giving rise to rough and de-pigmented eyes in freshly eclosed flies. In 50 h old (mid pupal stage) eye discs expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 the integrity of photoreceptor cells is poor when compared with wild-type pupal retina. Small vacuoles are present in Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 expressing retinas and the characteristic arrangement of the seven photoreceptors and the actin filaments within them are also altered. Unlike wild-type controls, flies overexpressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU do not show any significant phototaxis. Pan-neuronal overexpression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 via Scer\GAL4elav.PU results in 100% lethality at pupal stage.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF results in degeneration and depigmentation of the eye.
Flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 using Scer\GAL4GMR.PF show progressive eye degeneration, visualized by the presence of dark patches and collapsed eyes.
Pan-neural expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 (under the control of Scer\GAL4elav-C155) causes age-dependent neurodegeneration, as quantified by decreased numbers of Kenyon cells in the mushroom body.
Scer\GAL4GMR.PF-mediated expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 causes eye degeneration.
Expression of the Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in the adult eyes (under the control of an unknown Gal4 driver) show a rough eye phenotype.
Expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 in the eye under the control of Scer\GAL4GMR.PU results in eye degeneration, and patched, speckled, and collapsed eye phenotypes are observed.
Flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF display a rough-eye phenotype.
Expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 using Scer\GAL4GMR.PF induces substantial degeneration in eyes with loss of pigmentation and eye morphology. 2-day old flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 using Scer\GAL4GMR.PF fail to detect light.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in the developing eye, under the control of Scer\GAL4GMR.PF causes only a slight disruption of the regular, external lattice of the eye in young flies; however, the eye morphology of these flies shows progressive degeneration over time, with significant loss of pigmentation by day 15. Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4da.G32 in adult flies (using the temperature sensitive Scer\GAL80ts.αTub84B allele to limit expression) results in a shorter lifespan.
One day old flies expressing a strong insertion of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF show severe compound eye degeneration. This degeneration is strongly suppressed upon treatment with the HSF1-activating compound 17-AAG at concentrations of 500nM, 1.5µM and 5µM. Treatment at 50nM shows only a moderate therapeutic effect and treatment at 50µM has no effect. The suppression seen with 17-AAG is stronger than is seen with the histone deacetylase inhibitor SB, which shows only a weak effect. Treatment with GA at concentrations of 500nM and 5µM also results in modest suppression of compound eye degeneration, but no suppression is seen at concentrations of 500nM and 50µM. Treatment with RA at concentrations ranging from 50nM to 5µM also effectively suppresses neurodegeneration. No detectable changes are seen when the flies are treated with either CL (1 to 100 µM) or GGA (10µM to 40 mM). Expression of a strong insertion of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in the nervous system under the control of Scer\GAL4elav.PLu significantly decreases the survival rate of flies during their development to adults. This lethality is significantly suppressed upon treatment with the HSF1-activating compound 17-AAG. Eye discs from flies expressing a weak insertion of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF contain numerous inclusion bodies in the region posterior to the morphogenetic furrow. Significantly fewer inclusion bodies are seen when the flies are treated with the HSF1-activating compound 17-AAG and the size of the remaining inclusion bodies is significantly reduced. Treatment with 17-AAG also reduces the ratio of the anteroposterior width of the area with cells containing inclusion bodies to that of the area with cells containing diffusely distributed protein.
Expression of Scer\GAL4GMR.PF>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 results in severe rhabdomere degeneration.
Flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in the developing eye under the control of Scer\GAL4GMR.PF have a normal external eye, although internally the retina is disorganised. Flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in differentiated photoreceptor neurons under the control of Scer\GAL4ninaE.PD are born with the normal complement of seven visible photoreceptors per ommatidium, but progressive degeneration occurs, reducing the number of photoreceptors to on average 6.4 per ommatidium by 12 days and 3.7 by 18 days. Fewer neuron clones expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 (generated under the control of Scer\GAL4elav-C155 using MARCM) are retained compared to wild type. Only 13% are still detectable at 3 days and none are recovered at 6 days. This compares to an 83% recovery rate in controls. In retinal sections of animals expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in differentiated photoreceptor neurons under the control of Scer\GAL4ninaE.PD inclusions are sparse at 24h but prominent by 4 days.
One day old flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav-C155 show mild loss of retinal integrity, with approximately 5.8 photoreceptors per ommatidium, rather than the usual seven seen in controls. The lifespan of these flies is reduced compared to controls. Photoreceptor loss is also seen in 25 day old flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in differentiated photoreceptors under the control of Scer\GAL4ninaE.PD; these flies have on average 4.6 photoreceptors per ommatidium. Flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 pan-neuronally under the control of Scer\GAL4elav-C155 show normal climbing behaviour at one day old. Ability to climb becomes progressively worse with age, with approximately 42.1 percent of flies unable to climb by 12 days.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of both Scer\GAL4GMR.PF and Scer\GAL80ts.αTub84B induced in adult flies results in microscopic aggregates and degeneration in the eye. Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 transgene expression causes progressive deterioration of rhabdomere integrity from day 12 post induction.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU results in external and internal degeneration of the eye, with pigment loss and severely reduced retinal thickness. 1 day old flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU are functionally blind in a phototaxis assay, distributing randomly between a light and dark chamber.
Expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 driven by Scer\GAL4GMR.PF results in ablation of the adult eye.
50 day old flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav.PLu show almost no climbing activity.
Expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 in the eye (under the control of Scer\GAL4GMR.PF) induces degeneration, characterised by partial loss of pigmentation and retinal structure.
Expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1, under the control of Scer\GAL4GMR.PF, induces progressive degeneration of photoreceptors, coupled with the formation of protein aggregates in 2-day old flies.
Flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4tim.PE have no gross morphological abnormalities but show a significant decrease in lifespan and a significant decrease in mating activity during 1 hour observation periods, despite of an unaffected fertility, as compared to controls; expression of a 'strong' expression line of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 disables circadian locomotor activity patterns, but not the overall locomotor levels, and results in a significant decrease in the number of Pdf-positive small ventral latero-neurons, but not of Pdf-positive large ventral latero-neurons, as compared to controls. Expression of a 'strong' expression line of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4Ddc.PL causes no detectable circadian abnormality but does cause defects in female mating latency.
Expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 in the brain under the control of Scer\GAL430Y induces apoptotic neurodegeneration in the absence of cell cycle activation. Cortical neuron loss and neuropil rarefaction is observed in these animals. Expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 in the eye under the control of Scer\GAL4GMR.PF results in a rough-eye phenotype.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF results in roughened, depigmented eyes which contain black necrotic spots and are collapsed. Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav.Switch.PO in the presence of RU486 results in a reduction in adult life span compared to control flies (which have not been fed RU486).
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU leads to progressive degeneration and pigment loss in the adult eye.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav.PU, Scer\GAL4repo-M1B, or Scer\GAL4Appl.G1a leads to an insertion-dependent lethal phenotype, with the most severely affected line showing pupal lethality, and the less severely affected lines showing reduced adult lifespan. Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4repo-M1B, but not Scer\GAL4Appl.G1a, results in progressive neurodegeneration, with formation of vacuoles in the brain. Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4loco.PU leads to larval or pupal lethality. Flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4Appl.G1a or Scer\GAL4repo-M1B exhibit a progressive deficit in phototaxis, when under the control of Scer\GAL4repo-M1B (but not Scer\GAL4Appl.G1a) show progressive defects in walking speed and activity, as compared to controls.
Targeted expression of Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 in neurons using the Scer\GAL4elav-C155 driver results in early adult death. Ectopic expression of Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1, driven by Scer\GAL4GMR.PF, leads to late-onset degeneration in adult eyes. Eyes show loss of retinal structure and lack of pigment one day after eclosion.
Expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF results in severe degeneration of the retina that is associated with severe collapse of the eye. Co-expression of Hsap\MJDfl.Q27.Scer\UAS.T:Hsap\MYC restores the eye and retina phenotypes towards normal in flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF. Co-expression of Hsap\MJDtr.Q27.Scer\UAS.T:Ivir\HA1 does not suppress the eye degeneration phenotype caused by Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF. Co-expression of Hsap\MJDΔ.Scer\UAS.T:Hsap\MYC suppresses the eye degeneration phenotype caused by Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF. Co-expression of Hsap\MJDfl.Q27.UIMmut.Scer\UAS.T:Hsap\MYC partially suppresses the eye degeneration phenotype caused by Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF. Co-expression of Hsap\MJDfl.Q27.C14A.Scer\UAS.T:Hsap\MYC does not suppress the eye degeneration phenotype caused by Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF. Co-expression of Hsap\MJDfl.Q84.Scer\UAS.T:Hsap\MYC partially suppresses the eye degeneration phenotype caused by Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF.
Expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF results in a retinal degeneration phenotype. Expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL430Y results in a brain degeneration phenotype; neurons are present in normal numbers in 1 day old flies, but approximately 50% of Kenyon cells degenerate by 20 days after eclosion.
When Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 driven by Scer\GAL4elav-C155 nuclear aggregates are seen.
Animals expressing Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 driven by Scer\GAL4179Y or Scer\GAL4Appl.G1a exhibit a severe sluggish larval movement phenotype. A large increase in neuronal apoptosis is seen. When Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 is overexpressed at 29oC larvae do not survive to adulthood but die at second or third instar larval stage.
When Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 us driven by Scer\GAL4GMR.PF leads to severe, progressive eye degeneration contributing to abnormal ommatidium morphology.
Flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF have a severe eye degeneration phenotype, with loss of external and internal eye structure. The degeneration becomes more severe over the lifetime of the adult fly.
Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1; Scer\GAL4GMR.PF flies have an eye neurodegeneration phenotype.
Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU results in severe degeneration of the eye, with loss of external pigmentation and severe loss of photoreceptor cells in the retina. Weaker expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU results in a progressive degeneration of the retina as the adults age.
Strong expression of Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF results in a lack of eye pigmentation, indicating loss of pigment cells, and a collapsed eye, indicating loss of photoreceptor neurons. Weaker expression of Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF causes progressive degeneration of the eye during adult life.
Flies expressing Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF have degenerate eyes that lack pigment and show severe loss of retinal structure. Expression of Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav-C155 results in complete lethality or early adult death. Progressive degeneration of the eye, seen as disruption of the regular rhabdomere pattern, is seen.
Flies expressing Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF have rough eyes. The severity of the phenotype varies from mild roughness of the eye, through loss of pigment with severely disrupted eye morphology, to reduced eye size. The retina shows cell degeneration. The lamina and medulla show good structure and are normal in size, and the optic chiasm is present, even in flies with a severe phenotype. Large holes are visible in the most lateral part of the lamina, due to separation of the retinal basement membrane from the lamina in flies with moderate or severe phenotypes. The eye morphology progressively degenerates as the flies age. The retina does not deepen as much as normal in pupae expressing Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF. Pigmentation initiates at the correct time, but only occurs round the periphery of the developing eye. Flies expressing Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav-C155 emerge but show an early death phenotype in weak or moderate expressing P{UAS-Hsap\MJD.tr-Q78} lines. The brains of 4 day old flies appear shrunken compared to 1 day old flies, with the flies dying by 5 days. Gross degeneration of the brain is not seen. The eyes show some irregularity and loss of cell morphology of the rhabdomere lattice in 1 day old flies. A much greater loss of cell integrity is seen in 4 day old flies. Flies expressing Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav-C155 in strong expressing P{UAS-Hsap\MJD.tr-Q78} lines do not survive to adulthood. Flies expressing Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4how-24B die as embryos or larvae. Expression of Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4dpp.blk1 has no phenotypic effect.
External Data
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Hsap\ATXN3tr.Q78.UAS.Tag:HA, Scer\GAL4ninaE.PT has neuroanatomy defective | conditional phenotype, non-suppressible by Eip74EF[+]/Eip74EFBG01805
Hsap\ATXN3tr.Q78.UAS.Tag:HA, Scer\GAL4elav.Switch.PO has short lived | RU486 conditional phenotype, non-suppressible by Mlf[+]/MlfΔC1
Hsap\ATXN3tr.Q78.UAS.Tag:HA, Scer\GAL4elav.Switch.PO has short lived | RU486 conditional phenotype, non-suppressible by MlfΔ5-3/Mlf[+]
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Hsap\ATXN3tr.Q78.UAS.Tag:HA, Scer\GAL4ninaE.PD has photoreceptor | conditional phenotype, suppressible by Atx2X1/Atx2[+]
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Hsap\ATXN3tr.Q78.UAS.Tag:HA, Scer\GAL4ninaE.PT has adult brain | conditional phenotype, non-suppressible by Eip74EF[+]/Eip74EFBG01805
Hsap\ATXN3tr.Q78.UAS.Tag:HA, Scer\GAL4ninaE.PT has ommatidium | conditional phenotype, non-suppressible by Eip74EF[+]/Eip74EFBG01805
Hsap\ATXN3tr.Q78.UAS.Tag:HA, Scer\GAL4ninaE.PT has photoreceptor | conditional phenotype, non-suppressible by Eip74EF[+]/Eip74EFBG01805
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Xenogenetic Interactions
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The eye defects induced by the expression of Hsap\ATXN3tr.Q78.UAS.Tag:HA under the control of Scer\GAL4GMR.PU are aggravated by the co-expression of either Cul1GD9650, slmbNIG.3412R to the point of even leading to necrotic scars.
The rough eye phenotype and associated depigmentation and necrosis induced by the expression of Hsap\ATXN3tr.Q78.UAS.Tag:HA under the control of Scer\GAL4GMR.PF are severely exacerbated by the co-expression of embJF01311 or Kap-α3UASp.cMa, are slightly improved by the co-expression of cdmGS17666, embEY08770 or Kap-α3JF02686, but do not seem to be affected by the co-expression of cdmJF01428; the Kap-α3UASp.cMa co-expression condition also leads to prominent degeneration of the ommatidia. The late-onset eye defects (i.e. disorganized ommatidia and tissue dissociation associated with the appearance of vacuoles) induced by the expression of Hsap\ATXN3tr.Q78.UAS.Tag:HA under the control of Scer\GAL4ninaE.PT are mildly suppressed by the co-expression of Kap-α3JF02686, but do not seem to be affected by the co-expression of Kap-α3UASp.cMa.
The age-progressive eye pigmentation loss characteristic for adult flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU is not significantly affected by co-expression of either CG5445NIG.5445R or CG5445Scer\UAS.cUa.
The rough eye phenotype characteristic for adult flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU is not suppressed by expression of Usp8HMS01898.
Co-expression of Hsap\HSPA1LScer\UAS.cWa (but not Hsap\HSPA1LScer\UAS.sec, Hsc70-3Scer\UAS.cEa or Hsap\HSPA1LSBD-GY.Scer\UAS) completely suppresses the eye phenotypes of flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. Co-expression of Hsap\HSPA1LK71E.Scer\UAS.cFa or Hsap\HSPA1LSBD-GG.Scer\UAS enhances the eye phenotypes of flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU.
Co-expression of Hsp67BcScer\UAS.T:SV5\V5 (but not CG4461Scer\UAS.T:SV5\V5) significantly suppresses eye degeneration seen in flies with expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 driven by Scer\GAL4GMR.PF. Co-expression of Hsp67BcGD11244 significantly enhances eye degeneration phenotypes seen in flies with expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 driven by Scer\GAL4GMR.PF.
Co-expression of TgGD10774 exacerbates the Scer\GAL4GMR.PU>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 eye phenotype. TgGD10774 increases neuron death as well as the area affected by retinal collapse and loss of pigmentation. Co-expression of TgKK101591 exacerbates the Scer\GAL4GMR.PU>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 eye phenotype. TgKK101591 increases neuron death as well as the area affected by retinal collapse and loss of pigmentation. Co-expression of TgGD10774 with Scer\GAL4da.PU>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 exhibit results in a mild reduction if the lifespan of Scer\GAL4da.PU>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 flies. Co-expression of TgKK101591 with Scer\GAL4da.PU>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 exhibit results in a mild reduction if the lifespan of Scer\GAL4da.PU>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 flies. Co-expression of TgGD10774 with Scer\GAL4da.PU>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 exacerbates the locomotor activity defects in Scer\GAL4da.PU>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 flies. Co-expression of TgKK101591 with Scer\GAL4da.PU>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 exacerbates the locomotor activity defects in Scer\GAL4da.PU>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 flies. Overexpression of TgScer\UAS.T:Ivir\HA1 fails to mitigate the rough eye phenotype in Scer\GAL4GMR.PU>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1.
Co-expression of Rad23KK107826, DnaJ-1HMS00688, CG5001KK108978 or HsfJF02415 suppresses the protective role of expression of Hsap\ATXN3Scer\UAS.WT.T:Zzzz\His6 in suppressing eye degeneration in flies with Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 driven by Scer\GAL4GMR.long. Co-expression of effHM05268, CG9934JF02691, parkHMS01651, CG7220KK109208, STUB1HMS00986, sip3GD3145, Rpn8KK101319, Rpn11GD8888, Atg7GD11671, Atg8aHMS01328, Atg12JF02704, ref(2)PKK105338, mrjGD15063, CG7130GD2776, Hsc70-4JF03136, Hsc70-3HMS00397, CG10973KK104957, Hsp27HMS00807, Hsp60AKK107896, Hsp83HMS00796, simultaneous co-expression of Prosβ61.B.Scer\UAS and Prosβ21.Scer\UAS, or Prosβ61 does not suppress the protective role of expression of Hsap\ATXN3Scer\UAS.WT.T:Zzzz\His6 in suppression of eye degeneration in Scer\GAL4GMR.long>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 flies. Co-expression of effHM05268, CG9934JF02691, parkHMS01651, Hsc70-4JF03136 or Hsc70-3HMS00397 partially suppresses eye degeneration in Scer\GAL4GMR.long>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 flies. Co-expression of CG7220KK109208, STUB1HMS00986, sip3GD3145, Atg8aHMS01328, Atg12JF02704, ref(2)PKK105338, Atg7GD11671, DnaJ-1HMS00688, CG5001KK108978, CG7130GD2776 enhances eye degeneration in Scer\GAL4GMR.long>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 flies. Co-expression of Rpn8KK101319 or Rpn11GD8888, mrjGD15063 or Prosβ61 does not alter eye degeneration in Scer\GAL4GMR.long>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 flies. Simultaneous co-expression of Prosβ61.B.Scer\UAS and Prosβ21.Scer\UAS leads to lethality in Scer\GAL4GMR.long>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 flies; extra co-expression of Hsap\ATXN3Scer\UAS.WT.T:Zzzz\His6 suppresses this lethality. Co-expression of DnaJ-1Scer\UAS.cKa suppresses eye degeneration (external and internal) in flies (both 1 day and 2 weeks old) with expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 driven by Scer\GAL4GMR.long.
Co-expression of NosdsRNA.shRNA.Scer\UAS, NosJF03220, NosScer\UAS.cUa or p53JF02513 does not significantly alter neurodegeneration in flies with expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 driven by Scer\GAL4repo.PU.
Expression of TbpScer\UAS.cHa enhances the rough eye phenotype seen in the eyes of flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. The number of photoreceptors is also further reduced and there is an increase in aggregate formation. TbpsI10 enhances the photoreceptor loss seen in the eyes of flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. There is a reduction in the number of protein inclusions seen. TbpsI10 enhances the eye phenotypes seen when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed under the control of Scer\GAL4GMR.PU. The eyes appear glassy with large necrotic patches.
Reduction of Cdk5 transcript abundance, through the expression of Cdk5GD13840 does not affect the eye degeneration seen in eyes expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 (all transgenes under the control of Scer\GAL4GMR.long).
Expression of one copy of dominant-negative sggS9E.Scer\UAS in the developing eye, has no effect on toxicity due to expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1. However two copies of sggS9E.Scer\UAS partially suppresses Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1-induced eye depigmentation, with decreased black spots, more regular compound eye structure, and increased pigment cells. Expression of sggScer\UAS.cBa enhances the toxicity of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 flies (when both lines are expressed in the eye under the control of Scer\GAL4GMR.long. Flies expressing one copy of both lines exhibit serious eye depigmentation, including a greater loss of pigment cells, rough eye collapse, and a highly disordered ommatidial array. These defects are exacerbated by an additional copy of the sggScer\UAS.cBa transgene.
Expression of CHIPHMS00889 in the developing eye under the control of Scer\GAL4GMR.PF exacerbates the external eye degeneration caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1, highlighted by the presence of necrotic spots. Co-expression of Hsap\ATXN3Scer\UAS.T:Zzzz\His6 dramatically suppresses eye degeneration, despite expression of CHIPHMS00889.
The rough eye phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.long is suppressed by co-expression of Hsap\HSPA1LScer\UAS.cWa, but is not suppressed by co-expression of Hsap\TRAP1Scer\UAS.cBa.
Expression of mir-34Scer\UAS.cLa partially suppresses the degeneration seen when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed under the control of Scer\GAL4ninaE.PT. Inclusion formation is slowed, the protein retains greater solubility and neural degeneration is suppressed. The reduced number of photoreceptors per ommatidium seen in 21 day old flies is also partially rescued. One copy of Eip74EFBG01805 has little effect on the degeneration seen when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed under the control of Scer\GAL4ninaE.PT.
Co-expression of PlipGD4965 under the control of Scer\GAL4ninaE.PT has no significant effect on Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1-induced photoreceptor cell degradation. Co-expression of PlipKK108325 under the control of Scer\GAL4ninaE.PT has no significant effect on Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1-induced photoreceptor cell degradation.
Expression of BacA\p35Scer\UAS.cHa fails to suppress the dendrite phenotypes seen when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed in class IV da neurons under the control of Scer\GAL4ppk.PG. Expression of Rac1Scer\UAS.cLa partially suppresses the dendrite defects seen in class IV da neurons expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4ppk.PG. The reduction in F-actin structures in the distal dendrites of dorsal cluster neurons when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed under the control of Scer\GAL4109(2)80 is also partially rescued. Expression of Rac1V12.Scer\UAS further enhances the dendrite defects seen in class IV da neurons expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4ppk.PG. Expression of PakScer\UAS.T:Myr-Src64B partially suppresses the dendrite defects seen in class IV da neurons expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4ppk.PG. The reduction in F-actin structures in the distal dendrites of dorsal cluster neurons when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed under the control of Scer\GAL4109(2)80 is also partially rescued.
Expression of Mmus\PrnpP101L.Scer\UAS.T:Hsap\PRNP-3F4 significantly enhances the pathogenic eye defects seen upon expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 in the eye (both lines under the control of Scer\GAL4GMR.PF), with approximately 53% of ommatidia displaying aberrant structures.
Co-expression of Hsp60DdsRNA.Sym.Scer\UAS with Scer\GAL4GMR.PU-driven Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 suppresses the eye degeneration phenotype resulting from Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 overexpression. The eyes show normal pigmentation and more or less regularly organised ommatidial arrays nearly comparable to those in wild-type eyes. Co-expression of Hsp60DdsRNA.Sym.Scer\UAS with Scer\GAL4GMR.PU-driven Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 restores phototaxis. Co-expression of Hsp60DdsRNA.Sym.Scer\UAS via Scer\GAL4elav.PU partially suppresses the lethality resulting from Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 overexpression. The escapers are short lived with a maximum life span of six days. Co-expression of Pros261.Scer\UAS via Scer\GAL4elav.PU does not significantly affect the Hsp60DdsRNA.Sym.Scer\UAS-mediated partial suppression of the eye degeneration phenotype caused by Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 overexpression. The Hsp60DdsRNA.Sym.Scer\UAS-mediated suppression of the eye degeneration phenotype caused by Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 overexpression via Scer\GAL4GMR.PU is not much affected by heterozygosity for th5. Co-expression of Hsp60DdsRNA.Sym.Scer\UAS via Scer\GAL4GMR.PU fails to suppress the eye degeneration in Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 and thdsRNA.Scer\UAS expressing flies. The eye phenotype resulting from simultaneous expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 and Hsp60DdsRNA.Sym.Scer\UAS via Scer\GAL4GMR.PU does not appear to be affected by co-expression of Uba2C175S.Scer\UAS. The eye degeneration caused by Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 overexpression via Scer\GAL4GMR.PU is enhanced by co-expression of Pros261.Scer\UAS. Heterozygosity for th5 enhances the eye degeneration resulting from the overexpression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 via Scer\GAL4GMR.PU. Co-expression of thdsRNA.Scer\UAS via Scer\GAL4GMR.PU in Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1-expressing flies results in enhanced eye degeneration with reduction in eye size. Simultaneous expression of Uba2C175S.Scer\UAS and Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 via Scer\GAL4GMR.PU enhances eye degradation, resulting in more glazed eyes with little pigmentation.
Scer\GAL80Scer\FRT.αTub84B has no effect on the eye degeneration and depigmentation caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF. When FLPase is used to remove the Scer\FRT cassette in Scer\GAL80Scer\FRT.αTub84B, generating Scer\GAL80αTub84B.PB which expresses Scer\GAL80, the eye phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF is completely suppressed. Flies carrying Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1, Scer\GAL4GMR.PF and Scer\GAL80αTub84B.PG have normal eyes, due to repression of Scer\GAL4GMR.PF expression by Scer\GAL80αTub84B.PG. This repression can be removed using FLPase (which removes the Scer\FRT cassette containing the Scer\GAL80 coding region from Scer\GAL80αTub84B.PG).
Co-expression of Hsap\HSPB8Scer\UAS.WT or Hsp67BcScer\UAS.T:SV5\V5 significantly decreases the eye degeneration seen in Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1, Scer\GAL4GMR.PF flies. Co-expression of Hsp67BcGD11244 significantly worsens the eye degeneration seen in Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1, Scer\GAL4GMR.PF flies. Co-expression of Hsap\HSPB8Scer\UAS.K141E has no significant effect on the eye degeneration phenotype seen in Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1, Scer\GAL4GMR.PF flies. Co-expression of Hsap\HSPB8Scer\UAS.K141N significantly decreases the eye degeneration seen in Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1, Scer\GAL4GMR.PF flies.
Removing cathD from mutant Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 overexpressing flies (under the control of Scer\GAL4elav-C155 in a cathD1 background) has no effect on Kenyon cell loss.
Expression of nejF2161A.Scer\UAS.T:SV5\V5 in the Scer\GAL4GMR.PF, Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 background results in 15% lethality at the pupal stage. Surviving flies show a reduction in eye size and a greater disruption in ommatidial arrays. Additional co-expression of one copy of P{Sym-UAS-Hsrω} improves the eye morphology and size and reduces pupal death. Expression of nejdsRNA.Scer\UAS.cKa in the Scer\GAL4GMR.PF, Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 background results in >97% lethality at the pharate stage with eye degeneration being dramatically enhanced. Additional co-expression of P{Sym-UAS-Hsrω} robustly suppresses this enhanced eye damage, and also substantially reverses Scer\GAL4GMR.PF, Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 eye degeneration in a dose-dependent manner. Co-expression of P{Sym-UAS-Hsrω} also improves emergence to adult stage in a dose-dependent manner. The damaged eye phenotype that results from Scer\GAL4GMR.PF-mediated expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 is suppressed by co-expression of P{Sym-UAS-Hsrω}, and is not further enhanced by co-expression of Pros261.B.Scer\UAS and Prosβ21.Scer\UAS. Co-expression of P{Sym-UAS-Hsrω} still suppresses the damage in Scer\GAL4GMR.PF, Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1, Pros261.B.Scer\UAS, Prosβ21.Scer\UAS eyes, but the eyes are not rescued to the degree seen in Scer\GAL4GMR.PF, Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 eyes.
Expression of Hsap\HSPB7Scer\UAS.cVa in flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU suppresses the eye degeneration phenotype.
Expression of Hsap\MJDQ27.Scer\UAS.T:Hsap\MYC.T:Zzzz\FLAG in flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF suppresses the eye phenotype. Expression of Hsap\MJDQ84.Scer\UAS.T:Hsap\MYC.T:Zzzz\FLAG in flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF partially suppresses the eye phenotype. Expression of Hsap\MJD6M.Q83.Scer\UAS.T:Hsap\MYC.T:Zzzz\FLAG in flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF partially suppresses the eye phenotype.
Co-expression of two copies of P{Sym-UAS-Hsrω} almost completely suppresses the Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1, Scer\GAL4GMR.PF eye phenotype: the external appearance is wild type but rhabdomere arrays are still abnormal. Co-expression of one or two copies of P{Sym-UAS-Hsrω} restores normal phototactic behaviour to Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1, Scer\GAL4GMR.PF flies. Co-expression of a single copy of P{Sym-UAS-Hsrω} rescues the pharate lethality seen in Scer\GAL4elav-C155, Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 flies, allowing 94% of pupae to eclose. However, surviving female flies display abdominal swellings, and lifespan is reduced compared to controls.
The progressive degeneration of the eye caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF is suppressed by co-expression of either Rpn11DANC, Rpn11GS13423 or Rpn11Scer\UAS.cTa. Co-expression of Rpn11Scer\UAS.cTa partially suppresses the reduced lifespan caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4da.G32 during adulthood. Co-expression of Rpn11dsRNA.Scer\UAS enhances the progressive eye degeneration phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF.
Expression of HsfdsRNA.Scer\UAS suppresses the ability of the HSF1-activating compound 17-AAG to rescue the degeneration seen in flies expressing a strong insertion of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF. The amount of degeneration seen is similar to that observed in untreated flies. However, expression of HsfdsRNA.Scer\UAS also slightly enhances the compound eye degeneration in the absence of 17-AAG.
A marked suppression of Scer\GAL4GMR.PF>Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1-induced rhabdomere degeneration is observed when Hsap\GNB2L1Scer\UAS.cLa is co-expressed.
Co-expression of Atx2Scer\UAS.cSa and Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in the developing eye under the control of Scer\GAL4GMR.PF produces a more severe phenotype than in either mutant alone. The flies exhibit strong eye degeneration with loss of pigmentation and severe collapse of the retina. Co-expression of Atx2Scer\UAS.cSa and Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 in differentiated photoreceptor neurons under the control of Scer\GAL4ninaE.PD enhances the photoreceptor loss seen when either construct is expressed alone. Flies are still born with the normal complement of seven visible photoreceptors, but whereas at six days the single mutants appear near normal, co-expression results in only 4.7 photoreceptors per ommatidium. At 18 days almost complete photoreceptor loss (1.3 photoreceptors per ommatidium) is seen. One copy of Atx2X1 suppresses the eye degeneration seen when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed in differentiated photoreceptor neurons under the control of Scer\GAL4ninaE.PD. On average 6.9 visible photoreceptors are seen per ommatidium in 12 day old flies, similar to the 7 seen in controls. This compares to 6.4 when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed alone. Homozygous Atx2X1 suppresses the neuron loss seen in anterior wing margin clones induced in flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav-C155 (generated using MARCM). 77% of neurons are retained at 3 days, compared to only 13% when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed alone. 40% are recovered at 6 days, in contrast to the complete loss of neurons in Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 expressing flies. Expression of Atx2Scer\UAS.cSa enhances the rate of inclusion formation seen when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed in differentiated photoreceptor neurons under the control of Scer\GAL4ninaE.PD. Inclusions are more prominent at 24 hours, but by four days appear similar to when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed alone. Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 has no effect on the eye phenotype seen when Atx2ΔC1.Scer\UAS is expressed in the developing eye under the control of Scer\GAL4GMR.PF. The phenotype seen is identical to that seen when Atx2ΔC1.Scer\UAS is expressed alone. Co-expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 and Atx2ΔC1.Scer\UAS in differentiated photoreceptor neurons under the control of Scer\GAL4ninaE.PD causes mild photoreceptor loss at six days (an average of 6.7 visible photoreceptors per ommatidium, compared to seven in controls). This is similar to the phenotype seen when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed alone. Expression of Atx2ΔC1.Scer\UAS does not enhance the rate of inclusion formation seen when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed in differentiated photoreceptor neurons under the control of Scer\GAL4ninaE.PD. One copy of Df(2R)ED3610 enhances the photoreceptor loss seen when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed in differentiated photoreceptor neurons under the control of Scer\GAL4ninaE.PD. On average 1.6 photoreceptors are seen per ommatidium in 18 day old flies, as opposed to the seven seen in wild type. This compares to 3.5 when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed alone. Expression of pAbpScer\UAS.cSa partially suppresses the photoreceptor loss seen when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed in differentiated photoreceptor neurons under the control of Scer\GAL4ninaE.PD. On average 6.0 visible photoreceptors are seen per ommatidium in 18 day old flies, as opposed to the seven seen in wild type. This compares to 4.2 when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed alone.
Expression of mblScer\UAS.cLa enhances the reduction in lifespan and photoreceptor loss seen when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed pan-neuronally under the control of Scer\GAL4elav-C155. Flies have on average 3.0 photoreceptors per ommatidium, compared to the usual seven. One copy of mblE27 partially suppresses the shortened lifespan seen when Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 is expressed in the developing eye under the control of Scer\GAL4elav-C155.
Co-expression of BacA\p35Scer\UAS.cHa restores the Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 induced loss of rhabdomeres at day 12 post induction. However, the suppressive effect of BacA\p35Scer\UAS.cHa is lost at a later time point. Co-expression of BacA\p35Scer\UAS.cHa suppresses the Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 induced loss of rhabdomeres and significantly reduces the percentage of cells with aggregates. Co-expression of Hsap\HSPA1LScer\UAS.cWa can suppress neurodegeneration induced by Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1.
Hsp68E407, mrjE1050 and CG14207EP1348 are each strong suppressors of the eye degeneration phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. External eye pigmentation is restored, and the thickness of the retina is restored towards normal. DnaJ-1B345.2, DnaJ-1EP411, Tpr2EB7-1A, Ubp64EE213-1A, wechJM120, wechJM265, wechE546, wechEP2594, ImpEP1433 and CG5009B227.2 are each strong suppressors of the eye degeneration phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. CG11700EP1384, CG8209B3-Sa, FafE659, embE2-1A, embE128-1A, NFATEP1335 and NFATEP1508 are each moderate suppressors of the eye degeneration phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. Sin3AB9-E, dbrEP456, dbrEP9 and orb2B8-S are each weak suppressors of the eye degeneration phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. Kdm2EP3093 is an enhancer of the eye degeneration phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. Expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU in the presence of Df(3L)CH20/+ results in lethality and causes severe eye degeneration in pupae. Df(2L)r10 and Df(2L)PM44 each dominantly enhance the eye degeneration phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. Co-expression of mrjE1050 completely restores normal visual behaviour, and co-expression of CG14207EP1348 partially restores visual behaviour in 1 day old flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU and tested in a phototaxis assay. Co-expression of Prosβ61.B.Scer\UAS does not enhance the eye degeneration phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. In the presence of Prosβ61.B.Scer\UAS, CG11700EP1384 cannot suppress the eye degeneration phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. In the presence of Prosβ61.B.Scer\UAS, Ubp64EE213-1A cannot suppress the eye degeneration phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. DnaJ-1B345.2 and wechJM265 are each still able to suppress the eye degeneration phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU when the flies also carry Prosβ61.B.Scer\UAS.
The severe reduction in climbing ability seen in 50 day old flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav.PLu is partially suppressed by co-expression of one of TrxTScer\UAS.cUa, TrxTD26A.K57I.Scer\UAS, TrxTC35A.Scer\UAS, Trx-2Scer\UAS.cUa or dhdScer\UAS.cUa.
Eye degeneration due to expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 in the eye (under the control of Scer\GAL4GMR.PF) is enhanced in a loqsf00791 background, resulting in a severely degenerated eye with complete loss of pigmentation. Expression of banD.Scer\UAS.T:Avic\GFP-EGFP, bearing only a 100bp region containing the ban miRNA suppresses degeneration in Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 Scer\GAL4GMR.PF flies, restoring external and internal eye structures towards normal. Expression of banB.Scer\UAS.T:Avic\GFP-EGFP does not suppress eye degeneration in Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 Scer\GAL4GMR.PF flies. Eye degeneration due to expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 in the eye (under the control of Scer\GAL4GMR.PF) is enhanced in a Dcr-1Q1147X background, resulting in a severely degenerated eye with complete loss of pigmentation. Eye degeneration due to expression of Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 in the eye (under the control of Scer\GAL4GMR.PF) is unaffected by a Dcr-2L811fsX background. Co-expression of banB90.1 with Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 (under the control of Scer\GAL4GMR.PF gives normal pigementation and improved retinal structure.
Co-expression of Hsap\VCPScer\UAS.cBa with Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1, both under the control of Scer\GAL4GMR.PF fails to suppress the Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 photoreceptor phenotype in 2-day old flies.
The rough-eye phenotype observed in animals expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 in the eye under the control of Scer\GAL4GMR.PF is not modified by co-expression of RhebAV4. The rough-eye phenotype observed in animals expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 in the eye under the control of Scer\GAL4GMR.PF is not modified by co-expression of gigΔAkt-P.Scer\UAS.T:Zzzz\FLAG. The rough-eye phenotype observed in animals expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 in the eye under the control of Scer\GAL4GMR.PF is not modified by co-expression of dapScer\UAS.cdNa and RbfScer\UAS.cDa.
Co-expression of either MlfScer\UAS.cFa or MlfScer\UAS.cKa results in a strong suppression of the mutant eye phenotype caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF. The reduction in life span that is seen in flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav.Switch.PO in the presence of RU486 is partially rescued by co-expression of either MlfScer\UAS.cFa or MlfScer\UAS.cKa. The reduction in life span that is seen in flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav.Switch.PO in the presence of RU486 is not modified by the addition of MlfΔC1/+ or MlfΔ5-3/+.
The progressive degeneration and pigmentation loss eye phenotype characteristic for flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU is suppressed by co-expression of Hsap\HSPA1LScer\UAS.cWa although signs of degeneration are eventually observed in aged (32 days post-eclosion) flies. The eye degeneration phenotype is partially suppressed by co-expression of nejEP1410, is enhanced by co-expression of Hsc70-4K71S.Scer\UAS but not modified by combination with Hsp70Bc+t14 together with Hsp70Bb+t14.
The eye phenotype caused by expressing Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF, is not suppressed by coexpression of Hsap\BoatScer\UAS.T:Zzzz\FLAG.
Flies expressing both Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 and debclScer\UAS.T:Ivir\HA1 in their neurons, under the control of Scer\GAL4elav-C155, show a significantly shorter lifespan than flies expressing Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 alone. Coexpression of Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 and debclScer\UAS.T:Ivir\HA1, driven by Scer\GAL4GMR.PF, accelerates the onset of eye neurodegeneration seen in adults expressing Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1. The loss of retinal structure and pigment defects are strongly enhanced by debclScer\UAS.T:Ivir\HA1 expression. Overexpression of BuffyScer\UAS.cQa enhances the Scer\GAL4GMR.PF;Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1-induced eye neurodegeneration and lethality. Eyes coexpressing debclScer\UAS.T:Ivir\HA1, BuffyScer\UAS.cQa, and Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 (all driven by Scer\GAL4GMR.PF) show a significantly weaker degenerative eye phenotype than eyes expressing BuffyScer\UAS.cQa and Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1. Ectopic expression of debclGS2263, under the control of Scer\GAL4GMR.PF, suppresses the Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1-induced neurodegeneration of the eye. In addition , debclGS2263 markedly rescues the early adult death of flies expressing Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 in their neurons, driven by Scer\GAL4elav-C155.
Co-expression of Pros261.Scer\UAS suppresses the ability of Hsap\MJDfl.Q27.Scer\UAS.T:Hsap\MYC to restore the eye and retina phenotypes towards normal in flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF, such that the triple mutant flies have a reduction in eye pigmentation, show collapse of the eye and loss of internal retinal tissue.
When Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 is driven in neurons either by Scer\GAL4Appl.G1a or Scer\GAL4179Y, and combined with Khc9, mutant larval nerves contain axonal blockages. Mutant nerves also contain enlarged axons, some almost four or five times the diameter of those seen in wild-type. Sometimes "holes" lacking organelles are seen within the nerve.
Co-expression of Hsap\HSPA1LScer\UAS.cWa partially suppresses the eye degeneration seen in flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF. Co-expression of DnaJ-1Scer\UAS.T:Zzzz\FLAG partially suppresses the eye degeneration seen in flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF. Co-expression of both Hsap\HSPA1LScer\UAS.cWa and DnaJ-1Scer\UAS.T:Zzzz\FLAG completely suppresses the eye degeneration seen in flies expressing Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF.
The eye neurodegeneration phenotype of Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1; Scer\GAL4GMR.PF flies is not supressed by pucScer\UAS.cMa.
Co-expression of DnaJ-1Scer\UAS.T:Zzzz\FLAG restores external eye structure in animals expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. Internal eye structure is partially rescued, with partial preservation of photoreceptor rhabdomere specialisations. Co-expression of DnaJ-1Scer\UAS.T:Zzzz\FLAG slow the progressive retinal degeneration seen in flies that weakly express Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. Co-expression of either DnaJ-1ΔJ.Scer\UAS.T:Zzzz\FLAG or DnaJ-1G295D.Scer\UAS.T:Zzzz\FLAG enhances the weak eye phenotype seen in flies that weakly express Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU, such that loss of pigmentation and collapse of the eye is seen. Co-expression of DnaJ-HScer\UAS.T:Zzzz\FLAG only weakly suppresses the loss of eye pigmentation seen in flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. Expression of DnaJ-1Scer\UAS.T:Zzzz\FLAG cannot suppress the severe eye degeneration seen in flies co-expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 and Hsc70-4K71S.Scer\UAS under the control of Scer\GAL4GMR.PU. Flies that co-express Hsap\HSPA1LScer\UAS.cWa, Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 and DnaJ-1ΔJ.Scer\UAS.T:Zzzz\FLAG under the control of Scer\GAL4GMR.PU have normal eyes. Co-expression of Hsap\HSPA1LScer\UAS.cWa partially suppresses the retinal degeneration seen in flies expressing Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU. Simultaneous co-expression of both DnaJ-1Scer\UAS.T:Zzzz\FLAG and Hsap\HSPA1LScer\UAS.cWa results in a stronger suppression of the retinal degeneration caused by expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PU than expression of either construct alone.
The eye phenotype caused by expression of Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF is suppressed by coexpression of Hsap\HSPA1LScer\UAS.cWa; the eye appears normal externally, and internally eye structure is largely restored, although photoreceptor rhabdomere specialisations are not made. The eye degeneration phenotype caused by Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 expressed under the control of Scer\GAL4GMR.PF is not suppressed by coexpression of Hsap\MAPTScer\UAS.cAa or eyaScer\UAS.cBa. Adult viability in flies expressing Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav-C155 is partially restored by coexpression of Hsap\HSPA1LScer\UAS.cWa and degeneration of the eye is slowed. Hsc70-4K71S.Scer\UAS enhances the disruption of the eye caused by expression of Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF.
Co-expression of BacA\p35Scer\UAS.cHa in flies expressing Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR.PF partially restores eye pigmentation.
Complementation and Rescue Data
Comments
Co-expression of Hsap\ATXN3Scer\UAS.WT.T:Zzzz\His6 or Hsap\ATXN3HNHH.Scer\UAS.T:Zzzz\His6, but not Hsap\ATXN3C14A.Scer\UAS.T:Zzzz\His6, Hsap\ATXN3W87K.Scer\UAS.T:Zzzz\His6, significantly suppresses the eye degeneration (internal and external) seen in flies with expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 driven by Scer\GAL4GMR.long; co-expression of Hsap\ATXN3W87A.Scer\UAS.T:Zzzz\His6 partially suppresses the eye degeneration.
Co-expression of Hsap\ATXN3Scer\UAS.T:Zzzz\His6 dramatically suppresses the eye degeneration seen upon expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 (with both transgenes under the control of Scer\GAL4GMR.PF). Co-expression of Hsap\ATXN3C14A.Scer\UAS.T:Zzzz\His6 does not suppress the eye degeneration seen upon expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 (with both transgenes under the control of Scer\GAL4GMR.PF). Co-expression of Hsap\ATXN3K117.Scer\UAS.T:Zzzz\His6 suppresses the eye degeneration seen upon expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 (with both transgenes under the control of Scer\GAL4GMR.PF). Co-expression of non-ubiquitinatable Hsap\ATXN3K-null.Scer\UAS.T:Zzzz\His6 partially suppresses the eye degeneration seen upon expression of Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1 (with both transgenes under the control of Scer\GAL4GMR.PF). However, by 2 weeks of age the potency of Hsap\ATXN3K-null.Scer\UAS.T:Zzzz\His6 to suppress degeneration is markedly lower than that of Hsap\ATXN3Scer\UAS.T:Zzzz\His6 or Hsap\ATXN3K117.Scer\UAS.T:Zzzz\His6 transgenes. These flies still display severe eye degeneration and reduced retinal depth.
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Mutant
Wild-type
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Synonyms and Secondary IDs (5)
Reported As
Symbol Synonym
Hsap\ATXN3tr.Q78.Scer\UAS.T:Ivir\HA1
Hsap\ATXN3tr.Q78.UAS.Tag:HA
Hsap\MJDQ78.Scer\UAS.T:Ivir\HA1
Hsap\MJDQ78.UAS.T:HA1
Hsap\MJDtr.Q78.Scer\UAS.T:Ivir\HA1
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    References (83)