Open Close
General Information
Symbol
Hsap\HTTQ128.UAS
Species
H. sapiens
Name
FlyBase ID
FBal0156385
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
UAS-Htt-Q128, UAS-HttQ128, Htt-Q128, UAS-Htt548aa-128Q
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

UASt sequences drive expression of the N terminal 548 aa of the Q128 Hsap\HTT cDNA, which encodes the pathogenic protein.

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
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

The expression of Hsap\HTTQ128.UAS under the control of Scer\GAL4P2.4.Pdf severely impairs circadian behavior, and leads to a severe decrease in the number of sLNv nurons in 10-days old adults.

Most of the adult flies expressing Hsap\HTTQ128.Scer\UAS under the control of Scer\GAL4P2.4.Pdf show arrhythmic locomotor activity from the first day in constant darkness (DD) as well as poor consolidation of daily activity, whereas all control flies are rhythmic. The Hsap\HTTQ128.Scer\UAS-expressing flies have significantly fewer s-LNv somas that label positive for either Pdf or per, in contrast the number of Pdf-positive l-LNv neurons is comparable to controls but only about half of these is also positive for per. However, there is no significant difference in the number of Pdf+ s-LNv neurons between Hsap\HTTQ128.Scer\UAS-expressing flies that are (weakly) rhythmic and those completely arrhythmic and both these groups show Pdf immunoreactivity in the dorsal projections of s-LNv neurons. The Pdf levels in these dorsal projections oscillate after transfer to DD and while the peak coincides with the timing observed in control flies but the rise and fall of Pdf in Hsap\HTTQ128.Scer\UAS flies occurs earlier than in controls. per protein levels in the somas of l-LNv neurons do not oscillate and are very low relative to flies expressing Hsap\HTTQ0.Scer\UAS, whereas they oscillate with similar phase and overall intensity in other (Pdf-negative) neuronal groups (LNd, DN1, DN2 or the 5th s-LNv).

Adult flies expressing Hsap\HTTQ128.Scer\UAS continue to show anticipation of the dark-light transition even under low light intensity LD (light-dark) cycles and, like controls, show a clear oscillation in Pdf levels in s-LNv dorsal projections. On average, fewer per+ s-LNv somas are found in Hsap\HTTQ128.Scer\UAS expressing flies compared to Hsap\HTTQ0.Scer\UAS flies. The number of Pdf and per positive l-LNv somas are comparable between the two genotypes and in these neurons the per protein shows clear oscillation under LD although the amplitude is dampened in Hsap\HTTQ128.Scer\UAS flies compared to Hsap\HTTQ0.Scer\UAS.

Hsap\HTTQ128.Scer\UAS;Scer\GAL4P2.4.Pdf flies raised and maintained in constant light (LL) show a progressive loss of Pdf from s-LNv neurons' dorsal projections, flies maintained in LL, transferred to LD and then DD (the LL-LD regimen) show no Pdf+ s-LNv somas at age 23 and 28 days, not even after experiencing 5 days in LD. The numbers of Pdf+ l-LNv somas is comparable between regimens. Both LL-LD and LD-LD flies Scer\GAL4P2.4.Pdf>Hsap\HTTQ128.Scer\UAS flies exhibit activity profiles similar to their in-regimen controls and also show no differences in their morning and evening anticipation behavior relative to controls and across regimens.

Flies with expression of Hsap\HTTQ128.Scer\UAS driven by Scer\GAL4GMR.PU display a rough eye phenotype, with reduced numbers of ommatidia.

Expression of Hsap\HTTQ128.Scer\UAS under the control of Scer\GAL4GMR.PU results in a rough eye phenotype.

Expression of Hsap\HTTQ128.Scer\UAS under the control of Scer\GAL4elav.PLu results in time-dependent neurodegeneration. Newly eclosed flies have the normal complement of seven visible rhabdomeres per ommatidium, but this is reduced by day 10 post-eclosion. Treatment with meclizine partially rescues this phenotype.

Expression of Hsap\HTTQ128.Scer\UAS under the control of Scer\GAL4GMR.PU results in a loss of eye pigmentation, a rough eye phenotype and defects in the ommatidial array.

The loss of eye pigmentation seen in flies expressing Hsap\HTTQ128.Scer\UAS under the control of Scer\GAL4GMR.PU is significantly reduced by feeding with indomethacin.

Feeding with indomethacin increases the mean lifespan of flies expressing Hsap\HTTQ128.Scer\UAS under the control of Scer\GAL4elav.PU.

Expression of Hsap\HTTQ128.Scer\UAS under the control of an unknown Gal4 driver severely reduces adult survival rates.

One day old flies expressing Hsap\HTTQ128.Scer\UAS under the control of Scer\GAL4GMR.PF show photoreceptor degeneration, resulting in loss of rhabdomeres in each ommatidium. This photoreceptor degeneration is suppressed upon treatment with the HSF1-activating compound 17-AAG. Treatment with GA and RA modestly increases the number of rhabdomeres, as does the histone deacetylase inhibitor SB.

When Hsap\HDQ128.Scer\UAS is driven by Scer\GAL4GMR.PF a rough eye phenotype is seen. A loss of pigmentation is seen in the eye as well as abnormal bristle pattern and photoreceptor degeneration. A neurophysiological phenotype is also seen; mutant animals show reduced photoreceptor depolarisation and complete abolishment of synaptic transmission in response to light. Cytoplasmic Hsap\HD aggregates are seen in neurons, aggregates are transported in larval motor axons and accumulate in presynaptic neuromuscular junction terminals When Hsap\HDQ128.Scer\UAS is driven by Scer\GAL4elav-C155, larvae show a significant reduction in locomotor speed of about 25% from 1.23 mm/s to 0.92 mm/s. In adults expression of Hsap\HDQ128.Scer\UAS by Scer\GAL4elav-C155 cause adult lethality. When driven by Scer\GAL4elav.PLu adults are fully viable, however, several days after eclosion, mutant adults begin to exhibit uncoordinated movement and abnormal grooming behaviour. These behaviours worsen with age, resulting in premature death. When Hsap\HDQ128.Scer\UAS is driven by Scer\GAL4elav-C155, Hsap\HD cytoplasmic aggregates are seen in neurons. When driven by Scer\GAL4αTub84B.PL cytoplasmic aggregates are seen in both neuronal and non-neuronal tissues. No nuclear aggregates are seen.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
NOT Enhanced by
Suppressed by
Statement
Reference
NOT suppressed by
Statement
Reference

Hsap\HTTQ128.UAS, Scer\GAL4GMR.PU has visible | adult stage phenotype, non-suppressible by GIIIspla2EP1516/GIIIspla2[+]

Phenotype Manifest In
Enhanced by
Statement
Reference

Hsap\HTTQ128.UAS, Scer\GAL4GMR.PU has eye phenotype, enhanceable by rho-5[+]/rho-5KO1

Hsap\HTTQ128.UAS, Scer\GAL4GMR.PU has ommatidium phenotype, enhanceable by rho-5[+]/rho-5KO1

NOT Enhanced by
Statement
Reference
Suppressed by
NOT suppressed by
Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference

Co-expression of rho-5Scer\UAS.cZa or Hsap\RHBDF1Scer\UAS.cLa partially suppresses the rough eye phenotype and reduced numbers of ommatidia seen in flies with Hsap\HTTQ128.Scer\UAS driven by Scer\GAL4GMR.PU.

rho-5KO1/+ enhances the rough eye phenotype and reduced numbers of ommatidia seen in flies with Hsap\HTTQ128.Scer\UAS driven by Scer\GAL4GMR.PU.

One copy of GIIIspla2EP1516 does not suppress the rough eye phenotype seen when Hsap\HTTQ128.Scer\UAS is expressed under the control of Scer\GAL4GMR.PU.

Co-expression of slmbScer\UAS.cGa decreases the loss of eye pigmentation and improves ommatidial morphology in flies expressing Hsap\HTTQ128.Scer\UAS under the control of Scer\GAL4GMR.PU.

Complementation and Rescue Data
Comments
Images (0)
Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (4)
Reported As
Symbol Synonym
Hsap\HDQ128.Scer\UAS
Hsap\HTTQ128.Scer\UAS
Hsap\HTTQ128.UAS
Name Synonyms
Secondary FlyBase IDs
    References (18)