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General Information
Symbol
Hsap\HTT128Q.FL.UAS
Species
H. sapiens
Name
FlyBase ID
FBal0249417
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
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 drives expression of the entire 3144 amino acid Hsap\HTT protein with a pathogenic polyQ tract of 128 amino acids.

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 Ca-α1DX10
is ameliorated by Syx1AΔ229
is ameliorated by αSnapM4
is ameliorated by cacHC129
is ameliorated by RopG27
Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
 

Flies expressing Hsap\HTT128Q.FL.Scer\UAS pan-neuronally show interruption and fragmentation of nighttime sleep resembling that seen in human Huntington's Disease patients.

Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Expression of Hsap\HTT128Q.FL.Scer\UAS under the control of Scer\GAL4GMR.PU induces a rough eye phenotype in the adult eye.

Expression of Hsap\HTT128Q.FL.Scer\UAS under the control of Scer\GAL4Appl.G1a results in shorter adult lifespan and reduced climbing ability, although their flight performance is not strongly affected compared to control flies expressing Hsap\HTT16Q.FL.Scer\UAS.

Flies (recordings starting at 12 hours old) with expression of Hsap\HTT128Q.FL.Scer\UAS driven by Scer\GAL4elav.PU show a persistent decrease in night-time sleep and a significant increase in sleep latency within 4 days, compared to controls; night sleep is also more fragmented, with significant decreases in the average duration of sleep bouts and increases in the number of bouts at night, and flies show persistent night-time hyperactivity compared to controls by 5 days. Scer\GAL4elav.PU > Hsap\HTT128Q.FL.Scer\UAS flies show disturbed sleep homeostasis: after 12 hours of night-time sleep deprivation, daytime recovery trends lower than controls; post sleep deprivation, night-time sleep is not consolidated as in controls, with significantly lower average bout duration and significantly more bouts. Scer\GAL4elav.PU > Hsap\HTT128Q.FL.Scer\UAS flies do not show significant changes in geotactic behavior compared to controls. Sleep deprivation causes 5-10% lethality in mutants.

Expression of Hsap\HTT128Q.FL.Scer\UAS in the developing eye, under the control of Scer\GAL4GMR.long does not cause noticeable external eye degeneration in 1-day-old adults; by day 14, the external eye shows mild roughness in the periphery. Through histological studies, there are some signs of degeneration at day 1, highlighted by loss of definition of the ommatidial array. By day 14, there are marked signs of degeneration.

Flies expressing Hsap\HTT128Q.FL.Scer\UAS under the control of Scer\GAL4elav-C155 show reduced evoked excitatory junction potential (eEJP) amplitudes recorded at the third instar larval neuromuscular junction at 0.6 or 1.5 mM Ca[2+] concentrations compared to controls. Miniature excitatory junction potential m(EJP) amplitude distribution is shifted to the left compared to controls.

Flies expressing Hsap\HTT128Q.FL.Scer\UAS under the control of Scer\GAL4elav-C155 show reduced evoked excitatory junction potential (eEJP) amplitudes recorded at the third instar larval neuromuscular junction at 0.6 or 1.5 mM Ca[2+] concentrations compared to controls. Miniature excitatory junction potential (mEJP) amplitude is also reduced. mEJP decay kinetics, mEJP frequency and mean resting membrane potential are all unaffected.

Expression of Hsap\HTT128Q.FL.Scer\UAS under the control of Scer\GAL4elav-C155 results in rapid age-progressive decline in locomotor performance with limb tremors climbing speed.

Flies expressing Hsap\HTT128Q.FL.Scer\UAS under the control of Scer\GAL4elav.PU show sleep defects during the night that become more pronounced over the dark period. There is a significant reduction in total nighttime sleep and it is more fragmented (the duration of the average sleep bout and the length of the maximum sleep bout are decreased by 50% or more compared to controls and the number of sleep bouts is almost doubled). The number of daytime sleep bouts is decreased compared to controls, while average and maximum day sleep bout length and total daytime sleep are normal.

Expression of Hsap\HD128Q.FL.Scer\UAS using the strong Scer\GAL4GMR.PF driver results in depigmentation and disorganization of ommatidia.

Expression of Hsap\HD128Q.FL.Scer\UAS using a weaker Scer\GAL4GMR.PF driver does not disrupt rhabdomere organization in 1 day old flies. However, significantly fewer rhabdomeres per ommatidium are found in flies aged for 20 days, showing that this eye phenotype is progressive.

Flies expressing Hsap\HD128Q.FL.Scer\UAS using Scer\GAL4C164 show reduced survival in adult life compared to controls.

Flies expressing Hsap\HD128Q.FL.Scer\UAS using Scer\GAL4C164 show impaired motor performance as a function of age compared to controls, as measured by climbing and flying assays.

Aged flies expressing Hsap\HD128Q.FL.Scer\UAS using Scer\GAL4C164 show a neurodegenerative phenotype: motor neurons innervating the indirect flight muscles and neuromuscular junctions are lost.

Abnormalities in bouton number, branching or morphology are not observed in Hsap\HD128Q.FL.Scer\UAS, Scer\GAL4elav-C155 larvae.

Excitatory junction potentials (EJPs) at neuromuscular junctions of third instar larvae expressing Hsap\HD128Q.FL.Scer\UAS using Scer\GAL4elav-C155 are similar to controls at 1.2 mM extracellular Ca[2+], but are increased about 5-fold at 0.25 mM Ca[2+], and by ~30% at 0.6 mM Ca[2+].

Spontaneous fusion events at neuromuscular junctions in the absence of stimulation (mEJPs) in Hsap\HD128Q.FL.Scer\UAS, Scer\GAL4elav-C155 animals are similar in frequency and amplitude to controls.

The number of failures (non-events) when motor nerves are stimulated 2-3 times above threshold in 0.25 mM Ca[2+] in Hsap\HD128Q.FL.Scer\UAS, Scer\GAL4elav-C155 animals are very low - neurotransmitter is reliably released upon stimulation. This contrasts with controls which fail to release 20-25% of the time.

Resting synaptic Ca[2+] levels at presynaptic terminals are elevated by ~2-fold in Hsap\HD128Q.FL.Scer\UAS, Scer\GAL4elav-C155 larvae. In addition, Ca[2+] levels are more variable in these larvae compared to controls, with a bimodal distribution indicative of bouton populations with both normal and aberrant Ca[2+] levels.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Phenotype Manifest In
Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference

The rough eye phenotype characteristic for adult flies expressing Hsap\HTT128Q.FL.Scer\UAS under the control of Scer\GAL4GMR.PU is not suppressed by expression of Usp8HMS01898.

SnapM4/+, RopG27/+ or Syx1AΔ229/+ fully suppresses the increased excitatory junction potential (EJP) amplitude and decreased failure rate seen in Hsap\HD128Q.FL.Scer\UAS, Scer\GAL4elav-C155 animals at 0.25 mM Ca[2+].

Vha100-11/+ does not fully suppress the increased EJP amplitude seen in Hsap\HD128Q.FL.Scer\UAS, Scer\GAL4elav-C155 animals, and fails to suppress the increased release probability at 0.25 mM Ca[2+].

SnapM4/+, RopG27/+ or Syx1AΔ229/+ suppresses the reduced number of rhabdomeres per ommatidium phenotype seen in Hsap\HD128Q.FL.Scer\UAS, Scer\GAL4GMR.PF animals at 20 days. Vha100-11/+ does not suppress this phenotype.

Syx1AΔ229/+ suppresses the external eye phenotype seen in Hsap\HD128Q.FL.Scer\UAS, Scer\GAL4GMR.PF animals.

Syx1AΔ229/+ suppresses the impaired motor performance, as measured by a climbing assay, of Hsap\HD128Q.FL.Scer\UAS, Scer\GAL4C164 animals.

Syx1AΔ229/+ reverses the increase in resting synaptic Ca[2+] levels at presynaptic terminals seen in Hsap\HD128Q.FL.Scer\UAS, Scer\GAL4elav-C155 larvae.

Ca-α1DX10/+ reverses the increase in resting synaptic Ca[2+] levels at presynaptic terminals seen in Hsap\HD128Q.FL.Scer\UAS, Scer\GAL4elav-C155 larvae.

Ca-α1DX10/+ or cacHC129/+ significantly suppresses the increased excitatory junction potential (EJP) amplitude and decreased failure rate seen in Hsap\HD128Q.FL.Scer\UAS, Scer\GAL4elav-C155 animals at 0.25 mM Ca[2+].

Ca-α1DX10/+ suppresses the reduced number of rhabdomeres per ommatidium phenotype seen in Hsap\HD128Q.FL.Scer\UAS, Scer\GAL4GMR.PF animals at 20 days.

Complementation and Rescue Data
Comments
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Mutant
Wild-type
Stocks (2)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (3)
Reported As
Symbol Synonym
Hsap\HD128Q.FL.Scer\UAS
Hsap\HTT128Q.FL.Scer\UAS
Hsap\HTT128Q.FL.UAS
Name Synonyms
Secondary FlyBase IDs
    References (10)