FB2024_03 , released June 25, 2024
Allele: Hsap\HTT128Q.1-208.UAS
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General Information
Symbol
Hsap\HTT128Q.1-208.UAS
Species
H. sapiens
Name
FlyBase ID
FBal0249418
Feature type
allele
Associated gene
Hsap\HTT
Associated Insertion(s)
Carried in Construct
P{UAS-HTT.128Q.1-208}
Key Links
Transgenic product class
inframe_deletion
(Romero et al., 2008)
trinucleotide_repeat_expansion
(Romero et al., 2008)
Mutagen
Nature of the Allele
Transgenic product class
inframe_deletion
(Romero et al., 2008)
trinucleotide_repeat_expansion
(Romero et al., 2008)
Mutagen
in vitro construct
(Romero et al., 2008)
Progenitor genotype
Carried in construct
P{UAS-HTT.128Q.1-208}
Cytology
Description

UAS drives expression of the N-terminal amino acids 1-208 of Hsap\HTT protein with a pathogenic polyQ tract of 128 amino acids.

(Romero et al., 2008)
Allele components
Component
Use(s)
Regulatory region(s)
UAS
Encoded product / tool
Hsap\HTT
Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
Variant Molecular Consequences
Associated Sequence Data
DDBJ / EMBL / GenBank
DNA sequence
Protein sequence
 
UniProtKB/Swiss-Prot
    UniProtKB/TrEMBL
      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 )
      Disease
      Evidence
      References
      model of  Huntington's disease
      CEA
      (Gonzales et al., 2016, Gonzales and Yin, 2010)
      Modifiers Based on Experimental Evidence ( 1 )
      Disease
      Interaction
      References
      model of  Huntington's disease
      is ameliorated by Pka-C2KK110127
      (Gonzales et al., 2016)
      is ameliorated by Pka-C1KK108966
      (Gonzales et al., 2016)
      is ameliorated by Pka-R1BDK.UAS
      (Gonzales et al., 2016)
      Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
       

      Sleep disturbances are a clinical feature of Huntington's Disease. Flies expressing Hsap\HTT128Q.1-208.Scer\UAS pan-neuronally show fragmentation of nighttime sleep.

      (Gonzales and Yin, 2010)
      Disease-implicated variant(s)
       
      This allele represents a human variant implicated in disease.
      (Romero et al., 2008)
      HTT:p.Gln18[128]
      (FlyBase curators, 2019-)
      Variants Synonym(s)
      HTT:p.Gln18[128Gln]
      HTT, (CAG)n REPEAT EXPANSION
      Associated human disease model(s)
      External database links
      ClinVar: HTT_409
      Comments concerning this variant
      Phenotypic Data
      Phenotypic Class
      Phenotype Manifest In
      Detailed Description
      Statement
      Reference

      Flies (recordings starting at 12 hours old) with expression of Hsap\HTT128Q.1-208.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; sleep is more fragmented, with significant decreases in the average duration of sleep bouts during the day and night, and flies show persistent night-time hyperactivity compared to controls by 5 days. Scer\GAL4elav.PU > Hsap\HTT128Q.1-208.Scer\UAS flies show disturbed sleep homeostasis: after 12 hours of night-time sleep deprivation, flies have significantly decreased daytime sleep recovery compared to controls and show significant depression of night-time sleep; 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.1-208.Scer\UAS flies do not show significant changes in geotactic behavior compared to controls. Sleep deprivation causes 10-20% lethality in mutants. Position of the Hsap\HTT128Q.1-208.Scer\UAS insertion affects the severity of sleep phenotypes (F27B weaker, M64 stronger).

      Expression of Hsap\HTT128Q.1-208.Scer\UAS (weaker F27B insertion) driven by Scer\GAL4elav-C155 results in 85% lethality during metamorphosis; there is 100% (including earlier) lethality with the stronger M64 insertion.

      Expression of Hsap\HTT128Q.1-208.Scer\UAS (in the stronger M64 but not the weaker F27B insertion) driven by Scer\GAL4elav.PU leads to significant impairment of olfactory avoidance memory after three cycles of massed training, compared to controls; both insertions show normal learning.

      Expression of Hsap\HTT128Q.1-208.Scer\UAS (in both M64 and F27B) leads to a significantly shorter lifespan than controls.

      (Gonzales et al., 2016)

      Flies expressing Hsap\HTT128Q.1-208.Scer\UAS under the control of Scer\GAL4elav.PU show an increase in total daytime sleep and a decrease in total nighttime sleep within the first 5 days after eclosion compared to controls. The increase in daytime sleep is due to an increased number of sleep bouts without a significant change in duration. Nighttime sleep in these flies is fragmented compared to controls (there is an increased number of shorter sleep bouts). Activity is significantly reduced across the light:dark cycle in the mutant flies, including at light:dark transitions. These individuals also exhibit a significant decrease in adult lifespan, as compared to controls.

      (Gonzales and Yin, 2010)
      External Data
      Interactions
      Show genetic interaction network for Enhancers & Suppressors
      Phenotypic Class
      Suppressed by
      NOT suppressed by
      Phenotype Manifest In
      Additional Comments
      Genetic Interactions
      Statement
      Reference
      Xenogenetic Interactions
      Statement
      Reference

      Co-expression of Pka-R2GD15709 does not suppress lethality in flies with expression of Hsap\HTT128Q.1-208.Scer\UAS driven by Scer\GAL4elav-C155 (either the weak F27B or strong M64 insertion). Co-expression of Pka-C2KK110127 suppresses lethality in flies with expression of Hsap\HTT128Q.1-208.Scer\UAS driven by Scer\GAL4elav-C155 (both the weak F27B or strong M64 insertions), partially suppresses sleep homeostasis phenotypes (both insertions, expression driven by Scer\GAL4elav.PU) and significantly partially suppresses memory defects in the M64 line (expression driven by Scer\GAL4elav.PU). Co-expression of Pka-C1KK108966 suppresses lethality in flies with expression of Hsap\HTT128Q.1-208.Scer\UAS driven by Scer\GAL4elav-C155 (only delays lethality with the strong M64 insertion), and suppresses sleep phenotypes (tested F27B) (expression driven by Scer\GAL4elav.PU). Co-expression of Pka-R1BDK.Scer\UAS suppresses lethality in flies with expression of Hsap\HTT128Q.1-208.Scer\UAS driven by Scer\GAL4elav-C155 (only tested weak F27B insertion), and suppresses sleep and sleep homeostasis phenotypes (tested F27B) (expression driven by Scer\GAL4elav.PU). Co-expression of Pka-C1KK108966 or Pka-C2KK110127 significantly suppresses the shorter lifespan seen in Scer\GAL4elav.PU>Hsap\HTT128Q.1-208.Scer\UAS (F27B) flies; co-expression of Pka-C2KK110127 also suppresses the shorter lifespan seen in the M64 line.

      (Gonzales et al., 2016)
      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 (3)
      Reported As
      Symbol Synonym
      Hsap\HD128Q.1-208.Scer\UAS
      Hsap\HTT128Q.1-208.Scer\UAS
      Hsap\HTT128Q.1-208.UAS
      Name Synonyms
      Secondary FlyBase IDs
        References (4)