FlyBase Allele Report: Hsap\ATXN3[fl.Q84.UAS.Tag:MYC]

General Information

Symbol

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}

Species

H. sapiens

Name

FlyBase ID

FBal0196338

Feature type

allele

Associated gene

Hsap\ATXN3

Associated Insertion(s)

Carried in Construct

P{UAS-hATXN3.fl-Q84.myc}

Also Known As

SCA3-Q84, UAS-flMJD_CAG84

Key Links

Transgenic product class

trinucleotide_repeat_expansion

(Warrick et al., 2005)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

trinucleotide_repeat_expansion

(Warrick et al., 2005)

Mutagen

in vitro construct

(Warrick et al., 2005)

Progenitor genotype

Carried in construct

P{UAS-hATXN3.fl-Q84.myc}

Cytology

Description

UASt regulatory sequences drive expression of full-length Hsap\ATXN3 with a long polyQ repeat of Q84. The Hsap\ATXN3 sequence is tagged at the N-terminal end with Tag:MYC.

(Warrick et al., 2005)

Allele components

Component

Use(s)

Regulatory region(s)

UASt

binary expression system - regulatory region

Encoded product / tool

Hsap\ATXN3

Tagged with

Tag:MYC

epitope tag

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 neurodegenerative disease

CEA

(Burr et al., 2014, Bilen et al., 2006)

model of Machado-Joseph disease

CEA

(Chang et al., 2024, Zuniga et al., 2024, Nan et al., 2021, Chen et al., 2019, Wu et al., 2019, Chen et al., 2018, Vu et al., 2018, Yeh et al., 2018, Zhang et al., 2018, Fernius et al., 2017, Blount et al., 2014, Liman et al., 2014, Chan et al., 2011)

CEA with Hsap\ATXN3^{fl.Q27.UAS.Tag:MYC}

(Zhang et al., 2018)

model of autosomal dominant cerebellar ataxia

CEA

(Warrick et al., 2005)

CEC

(Boeddrich et al., 2006)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of neurodegenerative disease

is ameliorated by Hsap\ATXN3^{Scer\UAS.T:Zzzz\His6}

(Burr et al., 2014)

is ameliorated by Hsap\ATXN3^{UAS.Tag:polyHis}

(Burr et al., 2014)

is exacerbated by loqs^f00791

(Bilen et al., 2006)

model of Machado-Joseph disease

is ameliorated by emb^E128-1A

(Chan et al., 2011)

is exacerbated by emb^NIG.13387R

(Chan et al., 2011)

is exacerbated by Cdk5^GD13840

(Liman et al., 2014)

is ameliorated by Rad23^GD4245

(Blount et al., 2014)

is ameliorated by fy³

(Chen et al., 2018)

is ameliorated by fy^KK100638

(Chen et al., 2018)

is ameliorated by Su(var)2-10^JF01408

(Chang et al., 2024)

is ameliorated by Su(var)2-10^JF03384

(Chang et al., 2024)

is exacerbated by Cul1^GD9650

(Chen et al., 2019)

is exacerbated by FipoQ^NIG.2010R

(Chen et al., 2019)

is ameliorated by DnaJ-1^UAS.cKa

(Yeh et al., 2018)

is ameliorated by Hsap\DNAJC6^UAS.Tag:HA

(Yeh et al., 2018)

is ameliorated by Hsap\HSPA1L^UAS.cWa

(Yeh et al., 2018)

is ameliorated by Rac1^V12.UAS

(Vu et al., 2018)

model of autosomal dominant cerebellar ataxia

is ameliorated by Hsap\VCP^UAS.cBa

(Boeddrich et al., 2006)

Comments on Models/Modifiers Based on Experimental Evidence ( 0 )

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Warrick et al., 2005)

ATXN3:p.Gln296[84]

(FlyBase curators, 2019-)

Variants Synonym(s)

ATXN3:p.Gln296[84Gln]

ATXN3, (CAG)n REPEAT EXPANSION

Associated human disease model(s)

Machado-Joseph disease (SCA3)

External database links

ClinVar: ATXN3_209995

Comments concerning this variant

Phenotypic Data

Phenotypic Class

abnormal neuroanatomy, with Scer\GAL4^elav-C155

(Boeddrich et al., 2006)

abnormal neuroanatomy, with Scer\GAL4^GMR.PU

(Blount et al., 2014)

abnormal neuroanatomy | adult stage, with Scer\GAL4^GMR.PU

(Zhang et al., 2016)

abnormal neuroanatomy | progressive, with Scer\GAL4^elav-C155

(Liman et al., 2014)

abnormal phototaxis, with Scer\GAL4^GMR.PF

(Warrick et al., 2005)

abnormal phototaxis | adult stage, with Scer\GAL4^GMR.PU

(Bilen and Bonini, 2007)

increased cell death, with Scer\GAL4^GMR.PF

(Bilen et al., 2006)

short lived, with Scer\GAL4^elav.PU

(Zhang et al., 2016)

short lived, with Scer\GAL4^elav-C155

(Liman et al., 2014)

visible, with Scer\GAL4^GMR.PF

(Warrick et al., 2005)

visible | progressive, with Scer\GAL4^GMR.long

(Burr et al., 2014)

Phenotype Manifest In

eye, with Scer\GAL4^GMR.PF

(Bilen et al., 2006, Warrick et al., 2005)

eye | progressive, with Scer\GAL4^GMR.long

(Burr et al., 2014)

eye photoreceptor cell, with Scer\GAL4^elav-C155

(Boeddrich et al., 2006)

ommatidium | adult stage, with Scer\GAL4^GMR.PU

(Zhang et al., 2016)

ommatidium | progressive, with Scer\GAL4^GMR.long

(Burr et al., 2014)

retina, with Scer\GAL4^GMR.PF

(Bilen et al., 2006, Warrick et al., 2005)

retina, with Scer\GAL4^GMR.PU

(Blount et al., 2014)

retina | adult stage, with Scer\GAL4^GMR.PU

(Zhang et al., 2016)

rhabdomere, with Scer\GAL4^GMR.PF

(Chan et al., 2011)

rhabdomere of eye photoreceptor cell | adult stage, with Scer\GAL4^GMR.PU

(Zhang et al., 2016)

Detailed Description

Statement

Reference

Adults expressing Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC} under the control of Scer\GAL4^GMR.PU do not present any major eye defects.

(Chen et al., 2019)

Expression of Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4^GMR.PU leads to severe retinal degeneration, with a significant decrease in the number of rhabdomeres per ommatidium.

Expression of Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4^elav.PU leads to decreased lifespan.

(Zhang et al., 2016)

When Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC} is expressed selectively in fly eyes under the control of Scer\GAL4^GMR.PU, it does not greatly impact the external eye compared to wild-type controls. However, retinal sections show marked degeneration (disruption and loss of the radial ommatidial array and less-defined inter-ommatidial boundaries) and the presence of densely staining structures/aggregates, which contain pathogenic Hsap\ATXN3.

(Blount et al., 2014)

Expression of Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4^GMR.long does not generate obvious external eye defects after 14 days, despite the eye undergoing internal degeneration at this time. There is ommatidial loss and the presence of aggregates/inclusions.

(Burr et al., 2014)

Eye-specific expression of Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC}, under the control of Scer\GAL4^GMR.long results in almost no alteration in the external eye structure.

Pan-neural expression of Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC} (under the control of Scer\GAL4^elav-C155) results in a shortened lifespan, accompanied by neurodegeneration.

(Liman et al., 2014)

Expression of Hsap\MJD^{fl.Q84.Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4^GMR.PF results in a significant reduction in the number of rhabdomeres per ommatidium in newly eclosed flies compared to wild-type controls.

(Chan et al., 2011)

7 day old flies expressing Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4^GMR.PU have show strong vision defects in a phototaxis assay.

(Bilen and Bonini, 2007)

Expression of Hsap\MJD^{fl.Q84.Scer\UAS.T:Hsap\MYC} in the eye (under the control of Scer\GAL4^GMR.PF) causes mild retinal degeneration.

(Bilen et al., 2006)

Expression of Hsap\MJD^Q84.Scer\UAS, under the control of Scer\GAL4^elav-C155, induces progressive degeneration of photoreceptors, coupled with the formation of protein aggregates in 2-day old flies.

(Boeddrich et al., 2006)

Expression of Hsap\MJD^{fl.Q84.Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4^GMR.PF results in progressive adult-onset neural degeneration in the eye.

Flies expressing Hsap\MJD^{fl.Q84.Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4^GMR.PF are defective in phototaxis at 1 day after eclosion and are functionally blind by 4 days after eclosion. Co-expression of Hsap\MJD^{fl.Q27.Scer\UAS.T:Hsap\MYC} restores a normal phototaxis response in 4 day old flies expressing Hsap\MJD^{fl.Q84.Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4^GMR.PF.

Co-expression of Hsap\MJD^{fl.Q84.Scer\UAS.T:Hsap\MYC} partially suppresses the eye degeneration phenotype caused by Hsap\MJD^{tr.Q78.Scer\UAS.T:Ivir\HA1} under the control of Scer\GAL4^GMR.PF.

(Warrick et al., 2005)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^elav-C155 has short lived phenotype, enhanceable by Cdk5^GD13840, Scer\GAL4^elav-C155

(Liman et al., 2014)

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PF has increased cell death phenotype, enhanceable by loqs^f00791, Scer\GAL4^GMR.PF

(Bilen et al., 2006)

NOT Enhanced by

Statement

Reference

Cul1^GD9650, Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has visible | adult stage phenotype, non-enhanceable by FipoQ^NIG.2010R, Scer\GAL4^GMR.PU

(Chen et al., 2019)

FipoQ^NIG.2010R, Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has visible | adult stage phenotype, non-enhanceable by Cul1^GD9650, Scer\GAL4^GMR.PU

(Chen et al., 2019)

Suppressed by

Statement

Reference

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has abnormal neuroanatomy phenotype, suppressible by Rad23^GD4245, Scer\GAL4^GMR.PU

(Blount et al., 2014)

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has abnormal neuroanatomy phenotype, suppressible by Df(4)ED6369/+

(Blount et al., 2014)

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has abnormal phototaxis | adult stage phenotype, suppressible | partially by mrj^E1050, Scer\GAL4^GMR.PU

(Bilen and Bonini, 2007)

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has abnormal phototaxis | adult stage phenotype, suppressible | partially by CG14207^EP1348

(Bilen and Bonini, 2007)

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC} has abnormal neuroanatomy phenotype, suppressible by Scer\GAL4^elav-C155/Hsap\VCP^UAS.cBa

(Boeddrich et al., 2006)

NOT Enhancer of

Statement

Reference

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PF is a non-enhancer of visible phenotype of Atx2^UAS.cSa, Scer\GAL4^GMR.PF

(Lessing and Bonini, 2008)

Other

Statement

Reference

Cul1^GD9650, Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has visible | adult stage phenotype

(Chen et al., 2019)

FipoQ^NIG.2010R, Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has visible | adult stage phenotype

(Chen et al., 2019)

Atg5^RNAi.UAS, Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has abnormal neuroanatomy | adult stage phenotype

(Bilen and Bonini, 2007)

Phenotype Manifest In

Enhanced by

Statement

Reference

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PF has rhabdomere phenotype, enhanceable by emb^NIG.13387R, Scer\GAL4^GMR.PF

(Chan et al., 2011)

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PF has eye phenotype, enhanceable by loqs^f00791, Scer\GAL4^GMR.PF

(Bilen et al., 2006)

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PF has retina phenotype, enhanceable by loqs^f00791, Scer\GAL4^GMR.PF

(Bilen et al., 2006)

NOT Enhanced by

Statement

Reference

FipoQ^NIG.2010R, Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has eye phenotype, non-enhanceable by Cul1^GD9650, Scer\GAL4^GMR.PU

(Chen et al., 2019)

Cul1^GD9650, Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has eye phenotype, non-enhanceable by FipoQ^NIG.2010R, Scer\GAL4^GMR.PU

(Chen et al., 2019)

Suppressed by

Statement

Reference

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has retina phenotype, suppressible by Rad23^GD4245, Scer\GAL4^GMR.PU

(Blount et al., 2014)

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has retina phenotype, suppressible by Df(4)ED6369/+

(Blount et al., 2014)

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PF has rhabdomere phenotype, suppressible by emb^E128-1A, Scer\GAL4^GMR.PF

(Chan et al., 2011)

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC} has eye photoreceptor cell phenotype, suppressible by Scer\GAL4^elav-C155/Hsap\VCP^UAS.cBa

(Boeddrich et al., 2006)

NOT Enhancer of

Statement

Reference

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PF is a non-enhancer of eye phenotype of Atx2^UAS.cSa, Scer\GAL4^GMR.PF

(Lessing and Bonini, 2008)

Other

Statement

Reference

Cul1^GD9650, Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has eye phenotype

(Chen et al., 2019)

FipoQ^NIG.2010R, Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has eye phenotype

(Chen et al., 2019)

Cdk5^GD13840, Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.long has eye phenotype

(Liman et al., 2014)

Atg5^RNAi.UAS, Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Scer\GAL4^GMR.PU has retina phenotype

(Bilen and Bonini, 2007)

Additional Comments

Genetic Interactions

Statement

Reference

Xenogenetic Interactions

Statement

Reference

Adults co-expressing Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC} together with either Cul1^GD9650 or FipoQ^NIG.2010R, under the control of Scer\GAL4^GMR.PU, display mild eye depigmentation; this phenotype is not further enhanced by the triple co-expression of Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}, Cul1^GD9650 and FipoQ^NIG.2010R.

(Chen et al., 2019)

Expression of Scer\GAL4^GMR.PU>Rad23^GD4245 markedly suppresses retinal degeneration caused by Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC}-expression in fly eyes.

When Scer\GAL4^GMR.PU>Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC} is expressed in a Df(4)ED6369 hemizygous background, retinal degeneration is suppressed.

(Blount et al., 2014)

Reduction of Cdk5 transcript abundance, through the expression of Cdk5^GD13840 in eyes expressing Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC} (all transgenes under the control of Scer\GAL4^GMR.long) causes a disturbed eye surface and a loss of pigmentation.

RNAi-mediated Cdk5 reduction in Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC}-expressing flies (under the control of Scer\GAL4^elav-C155) results in an almost 50% reduction of median survival compared to controls.

(Liman et al., 2014)

Co-expression of emb^NIG.13387R enhances the loss of rhabdomere phenotype caused by expression of Hsap\MJD^{fl.Q84.Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4^GMR.PF. This enhancement is suppressed by co-expression of Hsap\HSPA1L^Scer\UAS.cWa.

Co-expression of emb^E128-1A suppresses the loss of rhabdomere phenotype caused by expression of Hsap\MJD^{fl.Q84.Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4^GMR.PF.

(Chan et al., 2011)

Expression of Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC} does not enhance the eye phenotypes seen when Atx2^Scer\UAS.cSa is expressed in the developing eye under the control of Scer\GAL4^GMR.PF.

Co-expression of Atx2^Scer\UAS.cSa and Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC} in differentiated photoreceptor neurons under the control of Scer\GAL4^ninaE.PD enhances the visible photoreceptor loss seen when either construct is expressed alone. At 18-23 days only 2.9 photoreceptors are seen per ommatidium, as opposed to the seven seen in wild type. This compares to 6.3 and 6.97 in Atx2^Scer\UAS.cSa and Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC} respectively.

(Lessing and Bonini, 2008)

Co-expression of mrj^E1050 or CG14207^EP1348 strongly suppresses the defects in phototaxis seen in 7 day old flies expressing Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4^GMR.PU.

Flies co-expressing Atg5^{dsRNA.Scer\UAS} and Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4^GMR.PU show loss of retinal integrity.

(Bilen and Bonini, 2007)

Eye degeneration due to expression of Hsap\MJD^{fl.Q84.Scer\UAS.T:Hsap\MYC} in the eye (under the control of Scer\GAL4^GMR.PF) is enhanced in a loqs^f00791 background, resulting in dramatically reduced retinal thickness.

(Bilen et al., 2006)

Co-expression of Hsap\VCP^Scer\UAS.cBa with Hsap\MJD^Q84.Scer\UAS, both under the control of Scer\GAL4^elav-C155, leads to a suppression of the Hsap\MJD^Q84.Scer\UAS photoreceptor degeneration phenotype in 2-day old flies.

(Boeddrich et al., 2006)

Complementation and Rescue Data

Partially rescued by

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC} is partially rescued by Hsap\ATXN3^{UAS.Tag:polyHis}/Scer\GAL4^GMR.long

(Burr et al., 2014)

Comments

Images (0)

Mutant

Wild-type

Stocks (1)

Bloomington

33610

w¹¹¹⁸; P{UAS-hATXN3.fl-Q84.myc}7.2/MKRS

Notes on Origin

Discoverer

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (4)

Reported As

Symbol Synonym

Hsap\ATXN3^{fl.Q84.Scer\UAS.T:Hsap\MYC}

Hsap\ATXN3^{fl.Q84.UAS.Tag:MYC}

Hsap\MJD^Q84.Scer\UAS

Hsap\MJD^{fl.Q84.Scer\UAS.T:Hsap\MYC}

Name Synonyms

Secondary FlyBase IDs

References (28)

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