FlyBase Allele Report: Hsap\HTT[128Q.FL.UAS]

General Information

Symbol

Hsap\HTT^128Q.FL.UAS

Species

H. sapiens

Name

FlyBase ID

FBal0249417

Feature type

allele

Associated gene

Hsap\HTT

Associated Insertion(s)

Carried in Construct

P{UAS-HTT.128Q.FL}

Also Known As

uas-htt.128Q.FL, UAS-HTT128Q

Key Links

Transgenic product class

trinucleotide_repeat_expansion

(Romero et al., 2008)

Mutagen

in vitro construct - regulatory fusion

Nature of the Allele

Transgenic product class

trinucleotide_repeat_expansion

(Romero et al., 2008)

Mutagen

in vitro construct - regulatory fusion

(Romero et al., 2008)

Progenitor genotype

Carried in construct

P{UAS-HTT.128Q.FL}

Cytology

Description

UASt drives expression of the entire 3144 amino acid Hsap\HTT protein with a pathogenic polyQ tract of 128 amino acids.

(Romero et al., 2008)

Allele components

Component

Use(s)

Regulatory region(s)

UASt

binary expression system - regulatory region

Encoded product / tool

Hsap\HTT

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)

model of Huntington's disease

CEA

(Swinter et al., 2023, Bolshakova et al., 2022, Casale et al., 2022, Xu et al., 2022, Migazzi et al., 2021, Beaver et al., 2020, Hope et al., 2020, White et al., 2020, Di Cristo et al., 2019, Tuxworth et al., 2019, Yeh et al., 2018, Billes et al., 2016, Steinert et al., 2012, Wu et al., 2011, Gonzales and Yin, 2010, Romero et al., 2008)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of Huntington's disease

is ameliorated by Ca-α1D^X10

(Romero et al., 2008)

is ameliorated by Syx1A^Δ229

(Romero et al., 2008)

is ameliorated by αSnap^M4

(Romero et al., 2008)

is ameliorated by cac^HC129

(Romero et al., 2008)

is ameliorated by Rop^G27

(Romero et al., 2008)

is ameliorated by Hap40^ko3

(Xu et al., 2022)

is ameliorated by Tip60^UAS.cUa

(Beaver et al., 2020)

is ameliorated by nbs¹

(Tuxworth et al., 2019)

is ameliorated by Su(var)3-9^UAS.EGFP

(Casale et al., 2022)

is ameliorated by Su(var)205^UASp.cCa

(Casale et al., 2022)

is ameliorated by Hsap\PRMT6^UAS.cSa

(Migazzi et al., 2021)

is ameliorated by Rab4^{UAS.mRFP(Unk)}

(White et al., 2020)

Comments on Models/Modifiers Based on Experimental Evidence ( 1 )

Flies expressing Hsap\HTT^{128Q.FL.Scer\UAS} pan-neuronally show interruption and fragmentation of nighttime sleep resembling that seen in human Huntington's Disease patients.

(Gonzales and Yin, 2010)

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Romero et al., 2008)

HTT:p.Gln18[128]

(FlyBase curators, 2019-)

Variants Synonym(s)

HTT:p.Gln18[128Gln]

HTT, (CAG)n REPEAT EXPANSION

Associated human disease model(s)

Huntington disease

External database links

ClinVar: HTT_409

Comments concerning this variant

Phenotypic Data

Phenotypic Class

abnormal eye color, with Scer\GAL4^GMR.PF

(Romero et al., 2008)

abnormal flight | conditional, with Scer\GAL4^C164

(Romero et al., 2008)

abnormal locomotor behavior | adult stage, with Scer\GAL4^Appl.G1a

(Billes et al., 2016)

abnormal locomotor behavior | adult stage | progressive, with Scer\GAL4^elav-C155

(Wu et al., 2011)

abnormal locomotor behavior | conditional, with Scer\GAL4^C164

(Romero et al., 2008)

abnormal neuroanatomy | adult stage, with Scer\GAL4^nSyb.PS

(Xu et al., 2022)

abnormal neurophysiology, with Scer\GAL4^elav-C155

(Romero et al., 2008)

abnormal neurophysiology | third instar larval stage, with Scer\GAL4^elav-C155

(Steinert et al., 2012)

abnormal sleep, with Scer\GAL4^elav.PU

(Gonzales et al., 2016, Gonzales and Yin, 2010)

decreased cell number | adult stage, with Scer\GAL4^nSyb.PS

(Xu et al., 2022)

increased cell death | larval stage, with Scer\GAL4^Appl.G1a

(Swinter et al., 2023)

increased rate of movement, with Scer\GAL4^elav.PU

(Gonzales et al., 2016)

short lived, with Scer\GAL4^Appl.G1a

(Billes et al., 2016)

short lived, with Scer\GAL4^C164

(Romero et al., 2008)

short lived, with Scer\GAL4^nSyb.PS

(Xu et al., 2022)

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

(Alexopoulou et al., 2016)

Phenotype Manifest In

Detailed Description

Statement

Reference

Expression of Hsap\HTT^{128Q.FL.Scer\UAS} under the control of Scer\GAL4^GMR.PU induces a rough eye phenotype in the adult eye.

(Alexopoulou et al., 2016)

Expression of Hsap\HTT^{128Q.FL.Scer\UAS} under the control of Scer\GAL4^Appl.G1a results in shorter adult lifespan and reduced climbing ability, although their flight performance is not strongly affected compared to control flies expressing Hsap\HTT^{16Q.FL.Scer\UAS}.

(Billes et al., 2016)

Flies (recordings starting at 12 hours old) with expression of Hsap\HTT^{128Q.FL.Scer\UAS} driven by Scer\GAL4^elav.PU show a persistent decrease in night-time sleep and a significant increase in sleep latency within 4 days, compared to controls; night sleep is also more fragmented, with significant decreases in the average duration of sleep bouts and increases in the number of bouts at night, and flies show persistent night-time hyperactivity compared to controls by 5 days. Scer\GAL4^elav.PU > Hsap\HTT^{128Q.FL.Scer\UAS} flies show disturbed sleep homeostasis: after 12 hours of night-time sleep deprivation, daytime recovery trends lower than controls; post sleep deprivation, night-time sleep is not consolidated as in controls, with significantly lower average bout duration and significantly more bouts. Scer\GAL4^elav.PU > Hsap\HTT^{128Q.FL.Scer\UAS} flies do not show significant changes in geotactic behavior compared to controls. Sleep deprivation causes 5-10% lethality in mutants.

(Gonzales et al., 2016)

Expression of Hsap\HTT^{128Q.FL.Scer\UAS} in the developing eye, under the control of Scer\GAL4^GMR.long does not cause noticeable external eye degeneration in 1-day-old adults; by day 14, the external eye shows mild roughness in the periphery. Through histological studies, there are some signs of degeneration at day 1, highlighted by loss of definition of the ommatidial array. By day 14, there are marked signs of degeneration.

(Burr et al., 2014)

Flies expressing Hsap\HTT^{128Q.FL.Scer\UAS} under the control of Scer\GAL4^elav-C155 show reduced evoked excitatory junction potential (eEJP) amplitudes recorded at the third instar larval neuromuscular junction at 0.6 or 1.5 mM Ca[2+] concentrations compared to controls. Miniature excitatory junction potential m(EJP) amplitude distribution is shifted to the left compared to controls.

Flies expressing Hsap\HTT^{128Q.FL.Scer\UAS} under the control of Scer\GAL4^elav-C155 show reduced evoked excitatory junction potential (eEJP) amplitudes recorded at the third instar larval neuromuscular junction at 0.6 or 1.5 mM Ca[2+] concentrations compared to controls. Miniature excitatory junction potential (mEJP) amplitude is also reduced. mEJP decay kinetics, mEJP frequency and mean resting membrane potential are all unaffected.

(Steinert et al., 2012)

Expression of Hsap\HTT^{128Q.FL.Scer\UAS} under the control of Scer\GAL4^elav-C155 results in rapid age-progressive decline in locomotor performance with limb tremors climbing speed.

(Wu et al., 2011)

Flies expressing Hsap\HTT^{128Q.FL.Scer\UAS} under the control of Scer\GAL4^elav.PU show sleep defects during the night that become more pronounced over the dark period. There is a significant reduction in total nighttime sleep and it is more fragmented (the duration of the average sleep bout and the length of the maximum sleep bout are decreased by 50% or more compared to controls and the number of sleep bouts is almost doubled). The number of daytime sleep bouts is decreased compared to controls, while average and maximum day sleep bout length and total daytime sleep are normal.

(Gonzales and Yin, 2010)

Expression of Hsap\HD^{128Q.FL.Scer\UAS} using the strong Scer\GAL4^GMR.PF driver results in depigmentation and disorganization of ommatidia.

Expression of Hsap\HD^{128Q.FL.Scer\UAS} using a weaker Scer\GAL4^GMR.PF driver does not disrupt rhabdomere organization in 1 day old flies. However, significantly fewer rhabdomeres per ommatidium are found in flies aged for 20 days, showing that this eye phenotype is progressive.

Flies expressing Hsap\HD^{128Q.FL.Scer\UAS} using Scer\GAL4^C164 show reduced survival in adult life compared to controls.

Flies expressing Hsap\HD^{128Q.FL.Scer\UAS} using Scer\GAL4^C164 show impaired motor performance as a function of age compared to controls, as measured by climbing and flying assays.

Aged flies expressing Hsap\HD^{128Q.FL.Scer\UAS} using Scer\GAL4^C164 show a neurodegenerative phenotype: motor neurons innervating the indirect flight muscles and neuromuscular junctions are lost.

Abnormalities in bouton number, branching or morphology are not observed in Hsap\HD^{128Q.FL.Scer\UAS}, Scer\GAL4^elav-C155 larvae.

Excitatory junction potentials (EJPs) at neuromuscular junctions of third instar larvae expressing Hsap\HD^{128Q.FL.Scer\UAS} using Scer\GAL4^elav-C155 are similar to controls at 1.2 mM extracellular Ca[2+], but are increased about 5-fold at 0.25 mM Ca[2+], and by ~30% at 0.6 mM Ca[2+].

Spontaneous fusion events at neuromuscular junctions in the absence of stimulation (mEJPs) in Hsap\HD^{128Q.FL.Scer\UAS}, Scer\GAL4^elav-C155 animals are similar in frequency and amplitude to controls.

The number of failures (non-events) when motor nerves are stimulated 2-3 times above threshold in 0.25 mM Ca[2+] in Hsap\HD^{128Q.FL.Scer\UAS}, Scer\GAL4^elav-C155 animals are very low - neurotransmitter is reliably released upon stimulation. This contrasts with controls which fail to release 20-25% of the time.

Resting synaptic Ca[2+] levels at presynaptic terminals are elevated by ~2-fold in Hsap\HD^{128Q.FL.Scer\UAS}, Scer\GAL4^elav-C155 larvae. In addition, Ca[2+] levels are more variable in these larvae compared to controls, with a bimodal distribution indicative of bouton populations with both normal and aberrant Ca[2+] levels.

(Romero et al., 2008)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^nSyb.PS has decreased cell number | adult stage phenotype, enhanceable by Hsap\F8A1^UAS.cXa, Scer\GAL4^nSyb.PS

(Xu et al., 2022)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^nSyb.PS has abnormal neuroanatomy | adult stage phenotype, enhanceable by Hsap\F8A1^UAS.cXa, Scer\GAL4^nSyb.PS

(Xu et al., 2022)

NOT Enhanced by

Statement

Reference

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^nSyb.PS has short lived phenotype, non-enhanceable by Hsap\F8A1^UAS.cXa, Scer\GAL4^nSyb.PS

(Xu et al., 2022)

Suppressed by

Statement

Reference

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^nSyb.PS has short lived phenotype, suppressible | partially by Hap40^ko3

(Xu et al., 2022)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^nSyb.PS has abnormal neuroanatomy | adult stage phenotype, suppressible | partially by Hap40^ko3

(Xu et al., 2022)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^nSyb.PS has decreased cell number | adult stage phenotype, suppressible | partially by Hap40^ko3

(Xu et al., 2022)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^elav-C155 has abnormal neurophysiology phenotype, suppressible by Snap[+]/αSnap^M4

(Romero et al., 2008)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^elav-C155 has abnormal neurophysiology phenotype, suppressible by Rop^G27/Rop[+]

(Romero et al., 2008)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^elav-C155 has abnormal neurophysiology phenotype, suppressible by Syx1A^Δ229/Syx1A[+]

(Romero et al., 2008)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^elav-C155 has abnormal neurophysiology phenotype, suppressible by Vha100-1¹/Vha100-1[+]

(Romero et al., 2008)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^elav-C155 has abnormal neurophysiology phenotype, suppressible by Ca-α1D^X10/Ca-alpha1D[+]

(Romero et al., 2008)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^elav-C155 has abnormal neurophysiology phenotype, suppressible by cac^HC129/cac[+]

(Romero et al., 2008)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^C164 has abnormal locomotor behavior | conditional phenotype, suppressible by Syx1A^Δ229/Syx1A[+]

(Romero et al., 2008)

NOT suppressed by

Statement

Reference

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^nSyb.PS has short lived phenotype, non-suppressible by Hsap\F8A1^UAS.cXa, Scer\GAL4^nSyb.PS

(Xu et al., 2022)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^GMR.PU has visible | adult stage phenotype, non-suppressible by Usp8^HMS01898, Scer\GAL4^GMR.PU

(Alexopoulou et al., 2016)

Phenotype Manifest In

Enhanced by

Statement

Reference

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^nSyb.PS has eye photoreceptor cell | adult stage | decreased number phenotype, enhanceable by Hsap\F8A1^UAS.cXa, Scer\GAL4^nSyb.PS

(Xu et al., 2022)

Suppressed by

Statement

Reference

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^nSyb.PS has eye photoreceptor cell | adult stage | decreased number phenotype, suppressible | partially by Hap40^ko3

(Xu et al., 2022)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^GMR.PF has rhabdomere of eye photoreceptor cell | conditional | adult stage phenotype, suppressible by Snap[+]/αSnap^M4

(Romero et al., 2008)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^GMR.PF has rhabdomere of eye photoreceptor cell | conditional | adult stage phenotype, suppressible by Syx1A^Δ229/Syx1A[+]

(Romero et al., 2008)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^GMR.PF has rhabdomere of eye photoreceptor cell | conditional | adult stage phenotype, suppressible by Rop^G27/Rop[+]

(Romero et al., 2008)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^GMR.PF has ommatidium | adult stage phenotype, suppressible by Syx1A^Δ229/Syx1A[+]

(Romero et al., 2008)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^GMR.PF has rhabdomere of eye photoreceptor cell | conditional | adult stage phenotype, suppressible by Ca-α1D^X10/Ca-alpha1D[+]

(Romero et al., 2008)

NOT suppressed by

Statement

Reference

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^GMR.PU has eye | adult stage phenotype, non-suppressible by Usp8^HMS01898, Scer\GAL4^GMR.PU

(Alexopoulou et al., 2016)

Hsap\HTT^128Q.FL.UAS, Scer\GAL4^GMR.PF has rhabdomere of eye photoreceptor cell | conditional | adult stage phenotype, non-suppressible by Vha100-1¹/Vha100-1[+]

(Romero et al., 2008)

Additional Comments

Genetic Interactions

Statement

Reference

Xenogenetic Interactions

Statement

Reference

The rough eye phenotype characteristic for adult flies expressing Hsap\HTT^{128Q.FL.Scer\UAS} under the control of Scer\GAL4^GMR.PU is not suppressed by expression of Usp8^HMS01898.

(Alexopoulou et al., 2016)

Snap^M4/+, Rop^G27/+ or Syx1A^Δ229/+ fully suppresses the increased excitatory junction potential (EJP) amplitude and decreased failure rate seen in Hsap\HD^{128Q.FL.Scer\UAS}, Scer\GAL4^elav-C155 animals at 0.25 mM Ca[2+].

Vha100-1¹/+ does not fully suppress the increased EJP amplitude seen in Hsap\HD^{128Q.FL.Scer\UAS}, Scer\GAL4^elav-C155 animals, and fails to suppress the increased release probability at 0.25 mM Ca[2+].

Snap^M4/+, Rop^G27/+ or Syx1A^Δ229/+ suppresses the reduced number of rhabdomeres per ommatidium phenotype seen in Hsap\HD^{128Q.FL.Scer\UAS}, Scer\GAL4^GMR.PF animals at 20 days. Vha100-1¹/+ does not suppress this phenotype.

Syx1A^Δ229/+ suppresses the external eye phenotype seen in Hsap\HD^{128Q.FL.Scer\UAS}, Scer\GAL4^GMR.PF animals.

Syx1A^Δ229/+ suppresses the impaired motor performance, as measured by a climbing assay, of Hsap\HD^{128Q.FL.Scer\UAS}, Scer\GAL4^C164 animals.

Syx1A^Δ229/+ reverses the increase in resting synaptic Ca[2+] levels at presynaptic terminals seen in Hsap\HD^{128Q.FL.Scer\UAS}, Scer\GAL4^elav-C155 larvae.

Ca-α1D^X10/+ reverses the increase in resting synaptic Ca[2+] levels at presynaptic terminals seen in Hsap\HD^{128Q.FL.Scer\UAS}, Scer\GAL4^elav-C155 larvae.

Ca-α1D^X10/+ or cac^HC129/+ significantly suppresses the increased excitatory junction potential (EJP) amplitude and decreased failure rate seen in Hsap\HD^{128Q.FL.Scer\UAS}, Scer\GAL4^elav-C155 animals at 0.25 mM Ca[2+].

Ca-α1D^X10/+ suppresses the reduced number of rhabdomeres per ommatidium phenotype seen in Hsap\HD^{128Q.FL.Scer\UAS}, Scer\GAL4^GMR.PF animals at 20 days.

(Romero et al., 2008)

Complementation and Rescue Data

Comments

Images (0)

Mutant

Wild-type

Stocks (2)

Bloomington

33808

w¹¹¹⁸; P{UAS-HTT.128Q.FL}f27b

33809

P{ActGFP}38, w¹¹¹⁸/C(1)DX, P{hs-hid}18A, y¹ w¹ f¹; P{UAS-HTT.128Q.FL}f27b

Notes on Origin

Discoverer

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (3)

Reported As

Symbol Synonym

Hsap\HD^{128Q.FL.Scer\UAS}

Hsap\HTT^{128Q.FL.Scer\UAS}

Hsap\HTT^128Q.FL.UAS

Name Synonyms

Secondary FlyBase IDs

References (25)

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