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General Information
Symbol
Hsap\ARQ52.UAS
Species
H. sapiens
Name
FlyBase ID
FBal0147861
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
AR52Q, UAS-AR52Q, UAS-hAR52Q
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

UAS regulatory sequences drive expression of human androgen receptor (Hsap\AR) in which the polyglutamine repeats are expanded from 20 to 52.

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 ( 3 )
 

Hsap\ARQ52.Scer\UAS disease model requires Hsap\AR ligand testosterone. Larvae raised in the presence of dihydroxytestosterone.

Disease phenotype requires presence of Hsap\AR ligand, dihydrotestosterone.

The degeneration phenotype caused by expression of Hsap\ARQ52.Scer\UAS is suppressed by rearing flies on the TOR inhibitor rapamycin.

Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Expression of Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PU results in degeneration of ommatidia on the posterior part of the compound eye.

When Hsap\ARQ52.Scer\UAS is expressed by the eye-specific driver Scer\GAL4GMR.PF, flies have a dihydrotestosterone (DHT)-dependent rough eye phenotype characterised by ommatidial degeneration and supernumerary interommatidial bristles, particularly in the posterior aspects of the eye. Rearing flies on media containing compound YM-1 alleviates the DHT-dependent eye degeneration in this line.

When Hsap\ARQ52.Scer\UAS is expressed in motor neurons by the Scer\GAL4BG380 or Scer\GAL4VGlut-OK371 driver lines, a significant percentage of flies fail to eclose in a DHT-dependent manner. The DHT-dependent pupal toxicity of Hsap\ARQ52.Scer\UAS-expression is significantly rescued by rearing flies on compound YM-1.

Expression of Hsap\ARQ52.Scer\UAS in motor neurons under the control of Scer\GAL4D42 in larvae fed on food supplemented with DHT, results in reduced motility of third instar larvae.

Whereas flies expressing Hsap\ARQ52.Scer\UAS in the developing eye under the control of Scer\GAL4GMR.PF show no eye phenotype when reared on normal food, flies reared on food containing dihydrotestosterone (DHT) exhibit a degenerative phenotype that is limited to the posterior margin of the eye. The severity of the phenotype is polyglutamine-length dependent, with Hsap\ARQ52.Scer\UAS expressing flies showing severe ommatidial pitting, disorganization, and fusion, as well as abnormal and supernumerary interommatidial bristles.

Expression of Hsap\ARQ52.Scer\UAS in the larval salivary gland under the control of Scer\GAL4fkh.PH in the presence of dihydrotestosterone results in a dramatic reduction in salivary gland size. Larvae expressing Hsap\ARQ52.Scer\UAS in motorneurons under the control of Scer\GAL4D42 in the presence of dihydrotestosterone exhibit defects in locomotor ability (as measured by larval crawling assay), indicating a significant functional deficit. In addition, the number of type 1B boutons at the larval neuromuscular junction is significantly decreased in a dihydrotestosterone-dependent manner when Hsap\ARQ52.Scer\UAS is expressed using the motor neuron driver Scer\GAL4VGlut-OK371.

Expression of Hsap\ARQ52.Scer\UAS in all neurons under the control of Scer\GAL4elav-C155 in the presence of dihydrotestosterone results in early lethality.

Flies expressing Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PU show an eye degeneration phenotype when raised on food containing 1mM dihydrotestosterone. This degeneration is suppressed if the food is also supplemented with 0.5mM Psammaplysene A.

Expression of Hsap\ARQ52.Scer\UAS in the developing eye under the control of Scer\GAL4GMR.PF does not generate a phenotype. However, expression in the presence of an active androgen (with 10[-5]M dehydrotestosterone) results in a rough eye phenotype.

Flies expressing Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PF in the absence of dihydrotestosterone (DHT) have normal eyes, but in the presence of DHT they have rough eyes.

Photoreceptor neurons show a significant increase in morphological features of autophagy in flies expressing Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PF in the presence of DHT; there is an increase in the number of autophagic vacuoles and in the number of multilamellar bodies/multivesicular bodies.

Transgenic flies carrying Hsap\ARQ52.Scer\UAS and Scer\GAL4GMR.PY show normal eye morphology. However, ingestion of the androgen receptor ligand dihydroxytestosterone (DHT) by these animals for 5 days after hatching induces marked disruption of the eye, including severely reduced ommatidium numbers and loss of pigmentation with thinned retinas in all lines tested at adult day 0. Treatment of these animals with the androgen antagonists hydroxyflutamide (HF) or bicalutamide (BIC), using the same regime as for DHT, results in even more extreme eye phenotypes than those caused by DHT treatment. Treatment of these animals with DHT or HF for 14 days after eclosion also causes severe rough eye phenotypes with loss of photoreceptor neurons, retina and pigmentation.

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

Co-expression of Art8KK107174, but not Art2GD10684 or Hsap\PRMT6Scer\UAS.cSa, partially suppresses the ommatidial degeneration seen in flies expressing Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PU.

The Hsap\ARQ52.Scer\UAS-induced toxicity is alleviated by the co-expression of Scer\GAL4VGlut-OK371>HIP-REY01382.

Larval motility defects observed in animals expressing Hsap\ARQ52.Scer\UAS in motor neurons under the control of Scer\GAL4D42 and fed on food supplemented with DHT, is enhanced in a ctpG0371 mutant background.

The presence of LmptGE27535 enhances the Hsap\ARQ52.Scer\UAS-Scer\GAL4GMR.PF degenerative eye phenotype.

A Dp(3;3)st+g18 background suppresses the degenerative eye phenotype found upon expression of Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PF.

Expression of LmptVDRC.cNa in flies expressing Hsap\ARQ52.Scer\UAS (both under the control of Scer\GAL4GMR.PF) enhances the Hsap\ARQ52.Scer\UAS degenerative eye phenotype.

The ability of 0.5mM Psammaplysene A to suppress the eye degeneration phenotype caused by expression of Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PU (in the presence of dihydrotestosterone) is suppressed if the flies are also heterozygous for one of foxoBG01018, foxo21, foxo25 or foxoc01841.

The presence of hoipGS7164 significantly enhances the neurodegeneration and rough eye phenotype seen upon expression of Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PF in the presence of 10[-5]M dehydrotestosterone. The numbers of rhabdomeres decreases significantly compared to single mutant controls.

The presence of nop5Scer\UAS.cMa significantly enhances the neurodegeneration and rough eye phenotype seen upon expression of Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PF in the presence of 10[-5]M dehydrotestosterone. The numbers of rhabdomeres decreases significantly compared to single mutant controls.

The presence of Nop56Scer\UAS.cMa significantly enhances the neurodegeneration and rough eye phenotype seen upon expression of Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PF in the presence of 10[-5]M dehydrotestosterone. The numbers of rhabdomeres decreases significantly compared to single mutant controls.

The rough eye phenotype seen in flies expressing Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PF in the presence of dihydrotestosterone (DHT) is suppressed by co-expression of HDAC6Scer\UAS.T:SV5\V5 or Hsap\HDAC6Scer\UAS.cPa, but not by co-expression of Hsap\HDAC6H216A.H611A.Scer\UAS.

The rough eye phenotype seen in flies expressing Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PF in the presence of dihydrotestosterone (DHT) is enhanced by co-expression of Atg6dsRNA.Scer\UAS or Atg12dsRNA.Scer\UAS.

The ability of HDAC6Scer\UAS.T:SV5\V5 to suppress the rough eye phenotype seen in flies expressing Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PF in the presence of dihydrotestosterone (DHT) is suppressed by co-expression of Atg12dsRNA.Scer\UAS.

DnaJ-1Scer\UAS.cKa partially suppresses the rough eye phenotype of Hsap\ARQ52.Scer\UAS; Scer\GAL4GMR.PY animals treated with the androgen receptor ligand dihydroxytestosterone (DHT).

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\ARQ52.Scer\UAS
Hsap\ARQ52.UAS
Name Synonyms
Secondary FlyBase IDs
    References (13)