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General Information
Symbol
Hsap\HTTGMR.Q120
Species
H. sapiens
Name
FlyBase ID
FBal0093286
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
gmr-Htt-Q120, gmr-HttQ120, GMR-HTT.Q120, gmr-Q120, Q120, gmr-Htt(exon1)Q120, GMR-HD.Q120
Key Links
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

Expression of Hsap\HTT amino acids 1-170, with 120 CAG glutamine repeats is governed by the GMR promoter.

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 ( 1 )
 

Aggregates form in the eyes of flies expressing Hsap\HTTGMR.Q120. Fewer aggregates are observed after treatment with compound SEN177.

Disease-implicated variant(s)
 
This allele represents a human variant implicated in disease.
HTT:p.Gln18[120]
Variants Synonym(s)
HTT:p.Gln18[120Gln]
HTT, (CAG)n REPEAT EXPANSION
Associated human disease model(s)
External database links
Comments concerning this variant
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Expression of Hsap\HTTGMR.Q120 results in neurodegeneration and the loss of rhabdomeres.

Flies expressing Hsap\HTTGMR.Q120 show a progressive decrease in the number of visible rhabdomeres per ommatidium.

The eyes of flies expressing Hsap\HTTGMR.Q120 progressively degenerate.

Flies expressing Hsap\HTTGMR.Q120 show strong age-dependent loss of rhabdomeres. Rhabdomeres that are present show accumulation of prominent vacuoles.

Newly eclosed flies carrying Hsap\HTTGMR.Q120 show degeneration of photoreceptor cells.

Fly photoreceptors that express Hsap\HTTGMR.Q120 exhibit degeneration. Neurodegeneration in these flies is progressive and associated with a decrease over time in the number of visible rhabdomeres in each ommatidium.

Flies expressing Hsap\HTTGMR.Q120 in the eye show degeneration of rhabdomeres. Low doses of N-acetyl cysteine (NAC) have no significant effect, while high doses exacerbated the neurodegenerative phenotype. Both NAC and cystamine significantly impairs the ability of rapamycin to rescue the neurodegenerative phenotype.

Expression of Hsap\HTTGMR.Q120 results in progressive rhabdomeric loss. Almost 7 rhabdomeres are observed within each ommatidium at day 2, but these are progressively lost with time.

Hsap\HTTGMR.Q120 flies manifest strong age-dependent loss of rhabdomeres and photoreceptor cells.

Flies expressing Hsap\HDGMR.Q120 show age-dependent degeneration of photoreceptors.

Flies expressing Hsap\HDGMR.Q120 show a marked reduction in the number of intact photoreceptors 2 days after eclosion.

Expression of Hsap\HTTGMR.Q120 results in loss of rhabdomeres 4 days after eclosion.

Hsap\HDGMR.Q120 expression results in photoreceptor cell degeneration.

Expression of Hsap\HDGMR.Q120 in the developing and adult eye, under the control of Scer\GAL4GMR.long severely disrupts photoreceptor neurons and ommatidial structure.

Hsap\HTTGMR.Q120 flies show age-dependent degeneration of rhabdomeres and photoreceptor cells compared to controls.

Flies show progressive loss of rhabdomeres. This phenotype can be partially rescued by rearing the animals on food containing Li[+] or AR-A014418.

10 day old flies expressing Hsap\HDGMR.Q120 show severe retinal degeneration.

The number of visible rhabdomeres in each ommatidium decreases over time in flies expressing mutant Hsap\HDGMR.Q120, while there is no reduction in the number of visible rhabdomeres in wild-type flies.

Hsap\HDGMR.Q120 leads to neurodegeneration in the eye.

Retinas expressing Hsap\HDGMR.Q120 still maintain the arrangement of the facets or ommatidia, indicated by the presence of hexagonal borders containing the darkly stained cirular forms of the photoreceptor rhabdomeres. However, after 1,2, or 5 weeks of age, the arrangement of ommatidia deteriorates.

Flies expressing Hsap\HTTGMR.Q120 have normal eyes at one day after eclosion, but show severe degeneration of the retina by 10 days of age.

Ommatidial morphology is normal at eclosion but at loss of rhabdomeres is apparent in ommatidia by 2 days after eclosion, and severe by 10 days after eclosion. By 10 days massive cell degeneration is evident in th ommatidia, with nuclear and cytoplasmic condensation, chromatin clumping and increased affinity for osmium. Subcellular organelles appear intact. Nuclear inclusions include distinct 40nm spherical particles, reminiscent of those induced by copia element.

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

Hsap\HTTGMR.Q120 has rhabdomere | conditional phenotype, suppressible | partially by Scer\GAL4sev.EP/panUAS.cWa

NOT suppressed by
Statement
Reference

Hsap\HTTGMR.Q120 has phenotype, non-suppressible by BacA\p35GMR.PH

Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference

Co-expression of Scer\GAL4GMR.PF>CalpAKK104532 partially suppresses the toxicity of Hsap\HTTGMR.Q120 in the eye.

Co-expression of CalpAKK104532 in an Atg8aKG07569 mutant genetic background exacerbates the toxicity of Hsap\HTTGMR.Q120 expression in the eye.

Expression of Hsap\HSPA1AScer\UAS.cTa in the pigment cells under the control of Scer\GAL454C partially suppresses the eye degeneration seen in flies expressing Hsap\HTTGMR.Q120. There is a significant increase in the number of rhabdomeres per ommatidium compared to Hsap\HTTGMR.Q120 alone.

Expression of Hsap\HSPA1AScer\UAS.cTa in either muscle (under the control of Scer\GAL4Mef2.PU) or fat body (using Scer\GAL4Lsp2.PH) partially suppresses the photoreceptor degeneration and reduction in the number of rhabdomeres per ommatidium seen in Hsap\HTTGMR.Q120 mutant flies.

Expression of Hsap\HSPA1AdS.Scer\UAS in either muscle (under the control of Scer\GAL4Mef2.PU) or fat body (using Scer\GAL4Lsp2.PH) does not suppress the photoreceptor degeneration and reduction in the number of rhabdomeres per ommatidium seen in Hsap\HTTGMR.Q120 mutant flies.

Expression of Ykt6dsRNA.Scer\UAS.cUa under the control of Scer\GAL4rdhB.PW does not suppress the eye degeneration seen in flies expressing Hsap\HTTGMR.Q120.

Expression of DnaJ-1Scer\UAS.cTa in photoreceptors under the control of Scer\GAL4GMR.PU suppresses the eye degeneration seen in flies expressing Hsap\HTTGMR.Q120.

Expression of DnaJ-1Scer\UAS.cTa in the pigment cells under the control of Scer\GAL454C partially suppresses the eye degeneration seen in flies expressing Hsap\HTTGMR.Q120. There is a significant increase in the number of rhabdomeres per ommatidium compared to Hsap\HTTGMR.Q120 alone. Expression under the control of another pigment cell driver, Scer\GAL4rdhB.PW, also suppresses the degeneration, and this suppression can be canceled out by co-expressing Ykt6dsRNA.Scer\UAS.cUa.

Expression of DnaJ-1Scer\UAS.cTa in either muscle (under the control of Scer\GAL4Mef2.PU or Scer\GAL4Mhc.PU) or fat body (using Scer\GAL4Lsp2.PH or Scer\GAL4r4) partially suppresses the photoreceptor degeneration seen in Hsap\HTTGMR.Q120 mutant flies. When DnaJ-1Scer\UAS.cTa and Ykt6dsRNA.Scer\UAS.cUa are co-expressed under the control of Scer\GAL4Lsp2.PH no suppression of the Hsap\HTTGMR.Q120 phenotype is seen.

Expression of DnaJ-1Scer\UAS.cKb under the control of Scer\GAL4GMR.PF slows the neural eye degeneration caused by expression of Hsap\HTTGMR.Q120. Some degeneration is observed at 10 days, and complete photoreceptor neuron loss is observed at 15 days.

Expression of Hsc70CbScer\UAS.cKa under the control of Scer\GAL4GMR.PF has no effect on neural eye degeneration caused by expression of Hsap\HTTGMR.Q120.

Hsc70CbScer\UAS.cKa suppresses the neural eye degeneration caused by seen when Hsap\HTTGMR.Q120 and DnaJ-1Scer\UAS.cKb are expressed under the control of Scer\GAL4GMR.PF. Essentially normal morphology is seen in the retinas of these flies at 10 days, although some degeneration is seen at 15 days.

Expression of Hsap\DNAJB1Scer\UAS.cKa under the control of Scer\GAL4GMR.PF does not suppress the photoreceptor loss phenotype seen upon expression of Hsap\HTTGMR.Q120. Complete loss of rhabdomeres and severe degeneration of photoreceptor cell is detected in the retinae of 7 day old flies.

Expression of Hsap\HSPA4LScer\UAS.cKa under the control of Scer\GAL4GMR.PF does not suppress the photoreceptor loss phenotype seen upon expression of Hsap\HTTGMR.Q120. Complete loss of rhabdomeres and severe degeneration of photoreceptor cell is detected in 7 day old flies.

Co-expression of Hsap\DNAJB1Scer\UAS.cKa and Hsap\HSPA4LScer\UAS.cKa under the control of Scer\GAL4GMR.PF partially suppresses the photoreceptor loss phenotype seen upon expression of Hsap\HTTGMR.Q120. Many normal photoreceptor cells are seen in the retinae of 7 day old flies.

Expression of Mmus\Xrcc6Scer\UAS.cTa under the control of Scer\GAL4GMR.long partially suppresses the photoreceptor degeneration seen in newly eclosed Hsap\HTTGMR.Q120 flies.

Overexpression of PsaGMR.Ex.PK in flies also expressing Hsap\HTTGMR.Q120 increases the number of visible photoreceptors.

Co-expression of Scer\GAL4elav-C155>PsaNIG.1009R enhances the toxicity of Hsap\HTTGMR.Q120.

Co-expression of Rpn11Scer\UAS.cTa (under the control of Scer\GAL4GMR.PF) suppresses the age-related rhabdomeric loss seen in flies expressing Hsap\HTTGMR.Q120.

Co-expression of Rpn11dsRNA.Scer\UAS (under the control of Scer\GAL4GMR.PF) enhances the age-related rhabdomeric loss seen in flies expressing Hsap\HTTGMR.Q120.

Polyglutamine aggregation is significantly enhanced when Rpn11dsRNA.Scer\UAS is expressed under the control of Scer\GAL4GMR.PF in Hsap\HTTGMR.Q120 flies.

Overexpression of Tsc1Scer\UAS.cGa or gigScer\UAS.cTa under the control of Scer\GAL4GMR.PU largely suppresses neural degeneration caused by expression of Hsap\HTTGMR.Q120.

Direct induction of autophagy through expression of Atg1ninaE.T:Hsap\MYC suppresses photoreceptor cell death in Hsap\HTTGMR.Q120 flies.

trpml1 enhances the rate of age-dependent degeneration of photoreceptors that is caused by expression of Hsap\HDGMR.Q120.

The loss of photoreceptors that is seen in flies expressing Hsap\HDGMR.Q120 is enhanced if the flies also carry one copy of Vps28D2, Vps25A3 or shrbG5.

Expression of Zzzz\Poly-AlaA37.Scer\UAS.T:Avic\GFP-EGFP,T:SV40\nls2 under the control of Scer\GAL4elav-C155 suppresses the loss of rhabdomeres seen when Hsap\HTTGMR.Q120 is expressed. An increase in visible rhabdomeres is seen at 1, 2 and 4 days post-eclosion.

Expression of Zzzz\Poly-AlaA7.Scer\UAS.T:Avic\GFP-EGFP,T:SV40\nls2 under the control of Scer\GAL4elav-C155 is unable to suppress the rhabdomere loss seen in flies expressing Hsap\HTTGMR.Q120.

Co-expression of Hsap\VCPScer\UAS.cBa, under the control of Scer\GAL4elav-C155, with Hsap\HDGMR.Q120 has no effect on the Hsap\HDGMR.Q120 eye degeneration phenotype.

Expression of Hsap\YAP1ΔC61.Scer\UAS in the developing and adult eye, under the control of Scer\GAL4GMR.long suppresses disruption of photoreceptor neurons and ommatidial structure in Hsap\HDGMR.Q120/Scer\GAL4GMR.long flies.

p535A-1-4/p535A-1-4 significantly partially suppresses age-dependent degeneration of rhabdomeres and photoreceptor cells in Hsap\HTTGMR.Q120 flies.

Heterozygosity for either arm1 or arm4 partially abolishes the protective effect of Li[+] with respect to photoreceptor loss in Hsap\HTTGMR.Q120 flies.

Expression of panScer\UAS.cWa under the control of Scer\GAL4sev.EP partially suppresses the loss of rhabdomeres seen in Hsap\HTTGMR.Q120 flies.

Heterozygosity for pan2 enhances the loss of rhabdomeres seen in Hsap\HTTGMR.Q120 flies.

Co-expression of Hsap\MJDfl.Q27.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav-C155 suppresses the retinal degeneration seen in 10 day old flies expressing Hsap\HDGMR.Q120.

The presence of one or two copies of MlfScer\UAS.cKa (with the Scer\GAL4GMR.PF driver) suppresses the deterioration of eye structure found in flies expressing Hsap\HDGMR.Q120.

Expression of Hsap\HSPA1LScer\UAS.cWa under the control of Scer\GAL4elav-C155 restores eye structure in 10 day old flies expressing Hsap\HTTGMR.Q120, such that photoreceptor neurons appear normal.

Expression of DnaJ-1Scer\UAS.T:Zzzz\FLAG under the control of Scer\GAL4elav-C155 only slightly suppresses the retinal degeneration seen in 10 day old flies expressing Hsap\HTTGMR.Q120.

Expression of DnaJ-HScer\UAS.T:Zzzz\FLAG does not suppress the retinal degeneration seen in 10 day old flies expressing Hsap\HTTGMR.Q120.

Complementation and Rescue Data
Comments
Images (0)
Mutant
Wild-type
Stocks (2)
Notes on Origin
Discoverer
Comments
Comments

Several lines containing Hsap\HDGMR.Q120 show somatic and germline instability.

External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (2)
Reported As
Symbol Synonym
Hsap\HDGMR.Q120
Hsap\HTTGMR.Q120
Name Synonyms
Secondary FlyBase IDs
    References (28)