FlyBase Allele Report: Hsap\AR[Q52.UAS]

General Information

Symbol

Hsap\AR^Q52.UAS

Species

H. sapiens

Name

FlyBase ID

FBal0147861

Feature type

allele

Associated gene

Hsap\AR

Associated Insertion(s)

Carried in Construct

P{UAS-Hsap\AR.Q52}

Also Known As

AR52Q, UAS-AR52Q, UAS-hAR52Q

Key Links

Transgenic product class

trinucleotide_repeat_expansion

(Takeyama et al., 2002)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

trinucleotide_repeat_expansion

(Takeyama et al., 2002)

Mutagen

in vitro construct

(Takeyama et al., 2002)

Progenitor genotype

Carried in construct

P{UAS-Hsap\AR.Q52}

Cytology

Description

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

(Takeyama et al., 2002)

Allele components

Component

Use(s)

Regulatory region(s)

UAS

binary expression system - regulatory region

Encoded product / tool

Hsap\AR

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 Kennedy's disease

CEA

(Badders et al., 2018, Nath et al., 2018, Scaramuzzino et al., 2015, Wang et al., 2012, Batlevi et al., 2010, Nedelsky et al., 2010, Palazzolo et al., 2010, Murata et al., 2008)

CEC

(Pandey et al., 2007)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of Kennedy's disease

is NOT ameliorated by Hsap\PRMT6^UAS.cSa

(Scaramuzzino et al., 2015)

is NOT ameliorated by Art2^GD10684

(Scaramuzzino et al., 2015)

is ameliorated by Art8^KK107174

(Scaramuzzino et al., 2015)

is exacerbated by Lmpt^GE27535

(Nedelsky et al., 2010)

is exacerbated by Lmpt^RNAi.UAS.cUa

(Nedelsky et al., 2010)

is exacerbated by ctp^G0371

(Batlevi et al., 2010)

is ameliorated by HIP-R^EY01382

(Wang et al., 2012)

is ameliorated by HDAC6^UAS.Tag:V5

(Pandey et al., 2007)

is exacerbated by Atg6^RNAi.UAS

(Pandey et al., 2007)

is exacerbated by Atg12^RNAi.UAS

(Pandey et al., 2007)

is ameliorated by Hsap\HDAC6^UAS.cPa

(Pandey et al., 2007)

is exacerbated by Rpn11^HMS00071

(Nath et al., 2018)

is exacerbated by Rpn13^GL01155

(Nath et al., 2018)

is exacerbated by cnc^HMS00650

(Nath et al., 2018)

is exacerbated by cnc^HMS02021

(Nath et al., 2018)

is exacerbated by cnc^JF02006

(Nath et al., 2018)

Comments on Models/Modifiers Based on Experimental Evidence ( 3 )

Hsap\AR^Q52.Scer\UAS disease model requires Hsap\AR ligand testosterone. Larvae raised in the presence of dihydroxytestosterone.

(Batlevi et al., 2010)

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

(Nedelsky et al., 2010)

The degeneration phenotype caused by expression of Hsap\AR^Q52.Scer\UAS is suppressed by rearing flies on the TOR inhibitor rapamycin.

(Pandey et al., 2007)

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Takeyama et al., 2002)

AR:p.Gln58[52]

(FlyBase curators, 2019-)

Variants Synonym(s)

AR:p.Gln58[52Gln]

AR, (CAG)n REPEAT EXPANSION

Associated human disease model(s)

spinal and bulbar muscular atrophy, X-linked 1

External database links

ClinVar: AR_417977

Comments concerning this variant

Phenotypic Data

Phenotypic Class

Phenotype Manifest In

autophagosome | increased number | drug conditional, with Scer\GAL4^GMR.PU

(Pandey et al., 2007)

eye, with Scer\GAL4^GMR.PF

(Nedelsky et al., 2010, Murata et al., 2008)

eye, with Scer\GAL4^GMR.PU

(Scaramuzzino et al., 2015)

eye | chemical conditional, with Scer\GAL4^GMR.PU

(Mojsilovic-Petrovic et al., 2009)

eye | drug conditional, with Scer\GAL4^GMR.PF

(Wang et al., 2012)

eye | drug conditional, with Scer\GAL4^GMR.PU

(Pandey et al., 2007)

eye | drug conditional, with Scer\GAL4^GMR.PY

(Takeyama et al., 2002)

eye photoreceptor cell | drug conditional, with Scer\GAL4^GMR.PU

(Pandey et al., 2007)

interommatidial bristle | increased number, with Scer\GAL4^GMR.PF

(Nedelsky et al., 2010)

interommatidial bristle | increased number | drug conditional, with Scer\GAL4^GMR.PF

(Wang et al., 2012)

multivesicular body | increased number | drug conditional, with Scer\GAL4^GMR.PU

(Pandey et al., 2007)

ommatidium, with Scer\GAL4^GMR.PF

(Nedelsky et al., 2010)

ommatidium, with Scer\GAL4^GMR.PU

(Scaramuzzino et al., 2015)

ommatidium | drug conditional, with Scer\GAL4^GMR.PF

(Wang et al., 2012)

ommatidium | drug conditional, with Scer\GAL4^GMR.PY

(Takeyama et al., 2002)

retina | drug conditional, with Scer\GAL4^GMR.PY

(Takeyama et al., 2002)

salivary gland, with Scer\GAL4^fkh.PH

(Nedelsky et al., 2010)

type I bouton, with Scer\GAL4^VGlut1-OK371

(Nedelsky et al., 2010)

Detailed Description

Statement

Reference

Expression of Hsap\AR^Q52.Scer\UAS under the control of Scer\GAL4^GMR.PU results in degeneration of ommatidia on the posterior part of the compound eye.

(Scaramuzzino et al., 2015)

When Hsap\AR^Q52.Scer\UAS is expressed by the eye-specific driver Scer\GAL4^GMR.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\AR^Q52.Scer\UAS is expressed in motor neurons by the Scer\GAL4^BG380 or Scer\GAL4^VGlut-OK371 driver lines, a significant percentage of flies fail to eclose in a DHT-dependent manner. The DHT-dependent pupal toxicity of Hsap\AR^Q52.Scer\UAS-expression is significantly rescued by rearing flies on compound YM-1.

(Wang et al., 2012)

Expression of Hsap\AR^Q52.Scer\UAS in motor neurons under the control of Scer\GAL4^D42 in larvae fed on food supplemented with DHT, results in reduced motility of third instar larvae.

(Batlevi et al., 2010)

Whereas flies expressing Hsap\AR^Q52.Scer\UAS in the developing eye under the control of Scer\GAL4^GMR.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\AR^Q52.Scer\UAS expressing flies showing severe ommatidial pitting, disorganization, and fusion, as well as abnormal and supernumerary interommatidial bristles.

Expression of Hsap\AR^Q52.Scer\UAS in the larval salivary gland under the control of Scer\GAL4^fkh.PH in the presence of dihydrotestosterone results in a dramatic reduction in salivary gland size. Larvae expressing Hsap\AR^Q52.Scer\UAS in motorneurons under the control of Scer\GAL4^D42 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\AR^Q52.Scer\UAS is expressed using the motor neuron driver Scer\GAL4^VGlut-OK371.

Expression of Hsap\AR^Q52.Scer\UAS in all neurons under the control of Scer\GAL4^elav-C155 in the presence of dihydrotestosterone results in early lethality.

(Nedelsky et al., 2010)

Flies expressing Hsap\AR^Q52.Scer\UAS under the control of Scer\GAL4^GMR.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.

(Mojsilovic-Petrovic et al., 2009)

Expression of Hsap\AR^Q52.Scer\UAS in the developing eye under the control of Scer\GAL4^GMR.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.

(Murata et al., 2008)

Flies expressing Hsap\AR^Q52.Scer\UAS under the control of Scer\GAL4^GMR.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\AR^Q52.Scer\UAS under the control of Scer\GAL4^GMR.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.

(Pandey et al., 2007)

Transgenic flies carrying Hsap\AR^Q52.Scer\UAS and Scer\GAL4^GMR.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.

(Takeyama et al., 2002)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

Hsap\AR^Q52.UAS, Scer\GAL4^Toll-6-D42 has abnormal locomotor behavior | conditional phenotype, enhanceable by ctp^G0371

(Batlevi et al., 2010)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has visible | drug conditional phenotype, enhanceable by Atg6^RNAi.UAS, Scer\GAL4^GMR.PU

(Pandey et al., 2007)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has visible | drug conditional phenotype, enhanceable by Atg12^RNAi.UAS, Scer\GAL4^GMR.PU

(Pandey et al., 2007)

Suppressed by

Statement

Reference

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has visible phenotype, suppressible | partially by Art8^KK107174, Scer\GAL4^GMR.PU

(Scaramuzzino et al., 2015)

Hsap\AR^Q52.UAS, Scer\GAL4^VGlut1-OK371 has partially lethal - majority live | drug conditional phenotype, suppressible | partially by HIP-R^EY01382, Scer\GAL4^VGlut1-OK371

(Wang et al., 2012)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has visible | drug conditional phenotype, suppressible by HDAC6^UAS.Tag:V5, Scer\GAL4^GMR.PU

(Pandey et al., 2007)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has visible | drug conditional phenotype, suppressible by Hsap\HDAC6^UAS.cPa, Scer\GAL4^GMR.PU

(Pandey et al., 2007)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PY has visible phenotype, suppressible | drug conditional | partially by DnaJ-1^UAS.cKa, Scer\GAL4^GMR.PY

(Takeyama et al., 2002)

NOT suppressed by

Statement

Reference

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has visible phenotype, non-suppressible by Art2^GD10684, Scer\GAL4^GMR.PU

(Scaramuzzino et al., 2015)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has visible phenotype, non-suppressible by Hsap\PRMT6^UAS.cSa, Scer\GAL4^GMR.PU

(Scaramuzzino et al., 2015)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has visible | drug conditional phenotype, non-suppressible by Hsap\HDAC6^{H216A.H611A.UAS}, Scer\GAL4^GMR.PU

(Pandey et al., 2007)

Phenotype Manifest In

Enhanced by

Statement

Reference

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PF has eye phenotype, enhanceable by Lmpt^GE27535, Scer\GAL4^GMR.PF

(Nedelsky et al., 2010)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PF has eye phenotype, enhanceable by Lmpt^RNAi.UAS.cUa, Scer\GAL4^GMR.PF

(Nedelsky et al., 2010)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PF has eye phenotype, enhanceable by hoip^GS7164, Scer\GAL4^GMR.PF

(Murata et al., 2008)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PF has rhabdomere phenotype, enhanceable by hoip^GS7164, Scer\GAL4^GMR.PF

(Murata et al., 2008)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PF has eye phenotype, enhanceable by nop5^UAS.cMa, Scer\GAL4^GMR.PF

(Murata et al., 2008)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PF has rhabdomere phenotype, enhanceable by nop5^UAS.cMa, Scer\GAL4^GMR.PF

(Murata et al., 2008)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PF has eye phenotype, enhanceable by Nop56^UAS.cMa, Scer\GAL4^GMR.PF

(Murata et al., 2008)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PF has rhabdomere phenotype, enhanceable by Nop56^UAS.cMa, Scer\GAL4^GMR.PF

(Murata et al., 2008)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has eye | drug conditional phenotype, enhanceable by Atg12^RNAi.UAS, Scer\GAL4^GMR.PU

(Pandey et al., 2007)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has eye | drug conditional phenotype, enhanceable by Atg6^RNAi.UAS, Scer\GAL4^GMR.PU

(Pandey et al., 2007)

Suppressed by

Statement

Reference

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has eye phenotype, suppressible | partially by Art8^KK107174, Scer\GAL4^GMR.PU

(Scaramuzzino et al., 2015)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has ommatidium phenotype, suppressible | partially by Art8^KK107174, Scer\GAL4^GMR.PU

(Scaramuzzino et al., 2015)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PF has eye phenotype, suppressible by Dp(3;3)st⁺g18

(Nedelsky et al., 2010)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has eye | drug conditional phenotype, suppressible by HDAC6^UAS.Tag:V5, Scer\GAL4^GMR.PU

(Pandey et al., 2007)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has eye | drug conditional phenotype, suppressible by Hsap\HDAC6^UAS.cPa, Scer\GAL4^GMR.PU

(Pandey et al., 2007)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PY has eye phenotype, suppressible | drug conditional | partially by DnaJ-1^UAS.cKa, Scer\GAL4^GMR.PY

(Takeyama et al., 2002)

NOT suppressed by

Statement

Reference

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has eye phenotype, non-suppressible by Art2^GD10684, Scer\GAL4^GMR.PU

(Scaramuzzino et al., 2015)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has ommatidium phenotype, non-suppressible by Art2^GD10684, Scer\GAL4^GMR.PU

(Scaramuzzino et al., 2015)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has eye phenotype, non-suppressible by Hsap\PRMT6^UAS.cSa, Scer\GAL4^GMR.PU

(Scaramuzzino et al., 2015)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has ommatidium phenotype, non-suppressible by Hsap\PRMT6^UAS.cSa, Scer\GAL4^GMR.PU

(Scaramuzzino et al., 2015)

Hsap\AR^Q52.UAS, Scer\GAL4^GMR.PU has eye | drug conditional phenotype, non-suppressible by Hsap\HDAC6^{H216A.H611A.UAS}, Scer\GAL4^GMR.PU

(Pandey et al., 2007)

Additional Comments

Genetic Interactions

Statement

Reference

Xenogenetic Interactions

Statement

Reference

Co-expression of Art8^KK107174, but not Art2^GD10684 or Hsap\PRMT6^Scer\UAS.cSa, partially suppresses the ommatidial degeneration seen in flies expressing Hsap\AR^Q52.Scer\UAS under the control of Scer\GAL4^GMR.PU.

(Scaramuzzino et al., 2015)

The Hsap\AR^Q52.Scer\UAS-induced toxicity is alleviated by the co-expression of Scer\GAL4^VGlut-OK371>HIP-R^EY01382.

(Wang et al., 2012)

Larval motility defects observed in animals expressing Hsap\AR^Q52.Scer\UAS in motor neurons under the control of Scer\GAL4^D42 and fed on food supplemented with DHT, is enhanced in a ctp^G0371 mutant background.

(Batlevi et al., 2010)

The presence of Lmpt^GE27535 enhances the Hsap\AR^Q52.Scer\UAS-Scer\GAL4^GMR.PF degenerative eye phenotype.

A Dp(3;3)st⁺g18 background suppresses the degenerative eye phenotype found upon expression of Hsap\AR^Q52.Scer\UAS under the control of Scer\GAL4^GMR.PF.

Expression of Lmpt^VDRC.cNa in flies expressing Hsap\AR^Q52.Scer\UAS (both under the control of Scer\GAL4^GMR.PF) enhances the Hsap\AR^Q52.Scer\UAS degenerative eye phenotype.

(Nedelsky et al., 2010)

The ability of 0.5mM Psammaplysene A to suppress the eye degeneration phenotype caused by expression of Hsap\AR^Q52.Scer\UAS under the control of Scer\GAL4^GMR.PU (in the presence of dihydrotestosterone) is suppressed if the flies are also heterozygous for one of foxo^BG01018, foxo²¹, foxo²⁵ or foxo^c01841.

(Mojsilovic-Petrovic et al., 2009)

The presence of hoip^GS7164 significantly enhances the neurodegeneration and rough eye phenotype seen upon expression of Hsap\AR^Q52.Scer\UAS under the control of Scer\GAL4^GMR.PF in the presence of 10[-5]M dehydrotestosterone. The numbers of rhabdomeres decreases significantly compared to single mutant controls.

The presence of nop5^Scer\UAS.cMa significantly enhances the neurodegeneration and rough eye phenotype seen upon expression of Hsap\AR^Q52.Scer\UAS under the control of Scer\GAL4^GMR.PF in the presence of 10[-5]M dehydrotestosterone. The numbers of rhabdomeres decreases significantly compared to single mutant controls.

The presence of Nop56^Scer\UAS.cMa significantly enhances the neurodegeneration and rough eye phenotype seen upon expression of Hsap\AR^Q52.Scer\UAS under the control of Scer\GAL4^GMR.PF in the presence of 10[-5]M dehydrotestosterone. The numbers of rhabdomeres decreases significantly compared to single mutant controls.

(Murata et al., 2008)

The rough eye phenotype seen in flies expressing Hsap\AR^Q52.Scer\UAS under the control of Scer\GAL4^GMR.PF in the presence of dihydrotestosterone (DHT) is suppressed by co-expression of HDAC6^{Scer\UAS.T:SV5\V5} or Hsap\HDAC6^Scer\UAS.cPa, but not by co-expression of Hsap\HDAC6^{H216A.H611A.Scer\UAS}.

The rough eye phenotype seen in flies expressing Hsap\AR^Q52.Scer\UAS under the control of Scer\GAL4^GMR.PF in the presence of dihydrotestosterone (DHT) is enhanced by co-expression of Atg6^{dsRNA.Scer\UAS} or Atg12^{dsRNA.Scer\UAS}.

The ability of HDAC6^{Scer\UAS.T:SV5\V5} to suppress the rough eye phenotype seen in flies expressing Hsap\AR^Q52.Scer\UAS under the control of Scer\GAL4^GMR.PF in the presence of dihydrotestosterone (DHT) is suppressed by co-expression of Atg12^{dsRNA.Scer\UAS}.

(Pandey et al., 2007)

DnaJ-1^Scer\UAS.cKa partially suppresses the rough eye phenotype of Hsap\AR^Q52.Scer\UAS; Scer\GAL4^GMR.PY animals treated with the androgen receptor ligand dihydroxytestosterone (DHT).

(Takeyama et al., 2002)

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 (2)

Reported As

Symbol Synonym

Hsap\AR^Q52.Scer\UAS

Hsap\AR^Q52.UAS

Name Synonyms

Secondary FlyBase IDs

References (14)

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