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General Information
Symbol
Hsap\HTTQ138.UAS.mRFP1
Species
H. sapiens
Name
FlyBase ID
FBal0267405
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
UAS-HttQ138-mRFP, UAS-RFP-HttQ138
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 588 amino acids of Hsap\HTT cDNA containing a pathogenic tract of 138 polyQ repeats. The construct is tagged at the N-terminal end with mRFP1.

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

Expression of Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP driven by Scer\GAL4Orco.PK only in adulthood (in combination with TubGAL80ts) leads to protein aggregates in olfactory receptor neuron terminals in 1 day old flies (but no evidence of cell death); after 15 days, cell death is evident in the central brain and optic lobes and after 30 days cell death is even more widespread.

Expression of Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP under the control of Scer\GAL4elav-C155 causes pharate adult lethality, with less than 1% viable adult escapers. Expression of Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP with a weaker elav-GAL4 driver (Scer\GAL4elav.PLu) results in viable adults that appear behaviourally normal at the time of eclosion. However, several days after eclosion these adults begin to exhibit motor coordination defects and abnormal grooming behaviours, worsening with age and resulting in premature death. The time taken for 50% of flies to die in the P{UAS-HTT.Q138.mRFP}A insertion line is 70% shorter than in controls, although this is reduced to 30% in the lower expressing P{UAS-HTT.Q138.mRFP}B insertion line.

Third instar larvae expressing Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP under the control of Scer\GAL4elav-C155 form distinct cytoplasmic aggregates throughout the cytoplasm and neurites of neurons in both the CNS and PNS. Expressing Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP ubiquitously under the control of Scer\GAL4αTub84B.PL shows that aggregates also form in non-neuronal cells, including epidermis and salivary glands. No nuclear aggregates were observed in any cell type. FRAP microscopy of live anaesthetised third instar larval axons expressing Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP under the control of Scer\GAL4Ccap.PP shows that the aggregates continue to accumulate protein following photobleaching, with larger aggregates recovering more quickly than smaller ones. Restricting Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP expression until the larvae reach the third instar larval stage shows that existing neuronal aggregates increase in size up to 12 hours, after which new aggregates begin to form. Restricting expression of Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP after aggregates have formed leads to a reduction in aggregate size and number.

Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP expressing neurons display morphological indicators of reduced neuronal health, including smaller neuromeres, increased branching, and reduced axonal connectivity.

Addition of rapamycin, 18β-Glycyrrhetinic acid, Carbenoxolone, Camptothecin or 10-Hydroxycamptothecin increases the longevity of larvae pan-neuronally expressing Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP under the control of Scer\GAL4elav-C155.

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

One copy of Df(3L)vin7 fully rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line. However the viable animals display motor defects, as they are unable to climb the walls of the vials or mate, and live to around 10 days post-eclosion.

One copy of Df(2L)JS17 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line. The viable animals display motor defects, as they are unable to climb the walls of the vials or mate, and most die within several days of eclosion.

One copy of Df(2R)cn9 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line. The viable animals display motor defects, as they are unable to climb the walls of the vials or mate, and most die within several days of eclosion.

One copy of Df(2R)AA21 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line. The viable animals display motor defects, as they are unable to climb the walls of the vials or mate, and most die within several days of eclosion.

One copy of Df(2R)59AD partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line. The viable animals display motor defects, as they are unable to climb the walls of the vials or mate, and most die within several days of eclosion.

One copy of Df(2L)BSC109 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line. The viable animals display motor defects, as they are unable to climb the walls of the vials or mate, and most die within several days of eclosion.

One copy of Df(3R)Tpl10 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line. The viable animals display motor defects, as they are unable to climb the walls of the vials or mate, and most die within several days of eclosion.

One copy of Df(3L)st-f13 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line. The viable animals display motor defects, as they are unable to climb the walls of the vials or mate, and most die within several days of eclosion.

One copy of Df(3L)brm11 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line. The viable animals display motor defects, as they are unable to climb the walls of the vials or mate, and most die within several days of eclosion.

One copy of Df(3R)H-B79 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line. The viable animals display motor defects, as they are unable to climb the walls of the vials or mate, and most die within several days of eclosion.

One copy of Df(3L)BSC33 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line. The viable animals display motor defects, as they are unable to climb the walls of the vials or mate, and most die within several days of eclosion.

One copy of Df(2R)59AD suppresses the Hsap\HTT aggregation seen in salivary glands when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the lower-expression P{UAS-HTT.Q138.mRFP}B insertion line. The number of axonal aggregates is not reduced.

One copy of Df(2R)AA21 suppresses the Hsap\HTT aggregation seen in salivary glands when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the lower-expression P{UAS-HTT.Q138.mRFP}B insertion line. The number of axonal aggregates is not reduced.

One copy of Df(2R)59AB suppresses the Hsap\HTT aggregation seen in salivary glands when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the lower-expression P{UAS-HTT.Q138.mRFP}B insertion line. The number of axonal aggregates is not reduced.

One copy of Df(2R)59AB partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line.

One copy of Df(2R)cn9 suppresses the Hsap\HTT aggregation seen in salivary glands when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the lower-expression P{UAS-HTT.Q138.mRFP}B insertion line. The number of axonal aggregates is not reduced.

One copy of Df(2R)sple-J1 suppresses the Hsap\HTT aggregation seen in salivary glands when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the lower-expression P{UAS-HTT.Q138.mRFP}B insertion line. The number of axonal aggregates is not reduced.

One copy of Df(2R)sple-J1 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line.

One copy of Df(3L)vin7 suppresses the Hsap\HTT aggregation seen in salivary glands when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the lower-expression P{UAS-HTT.Q138.mRFP}B insertion line. The number of axonal aggregates is also reduced.

One copy of Df(3L)ED220 significantly rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line.

One copy of Df(3R)MAP117 significantly rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line.

One copy of Df(3R)MAP2 significantly rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line.

One copy of CG5830c02324 rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line. The number of axonal aggregates seen in the peripheral nerves of third instar larvae is not reduced.

One copy of lab14 significantly rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line. The number of axonal aggregates seen in the peripheral nerves of third instar larvae is not reduced.

One copy of ScrCP1 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line.

One copy of Scr6 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line.

One copy of pb1 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line.

One copy of Dfd6 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line.

One copy of Ubx51 partially rescues the lethality seen when Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP is expressed under the control of Scer\GAL4elav-C155 using the P{UAS-HTT.Q138.mRFP}A insertion line.

lkb14B1-11 or lkb14A4-2 heterozygous animals expressing Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP pan-neuronally (under the control of Scer\GAL4elav-C155) exhibit an adult escaper frequency of 1.8% and 3.7% respectively. These animals are viable and have a relatively normal walking ability, although they do not inflate their wings.

The introduction of an lkb14A4-2 heterozygous background enhances the climbing ability of flies expressing Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP under the control of Scer\GAL4elav-C155. However, this has no effect on controls.

Complementation and Rescue Data
Comments
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Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (2)
Reported As
Symbol Synonym
Hsap\HTTQ138.Scer\UAS.T:Disc\RFP-mRFP
Hsap\HTTQ138.UAS.mRFP1
Name Synonyms
Secondary FlyBase IDs
    References (11)