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General Information
Symbol
Hsap\APPArctic.UAS.Tag:SS(nec)
Species
H. sapiens
Name
FlyBase ID
FBal0248069
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
UAS-ArcAβ42, UAS-Arctic Aβ42, AlzArc, UAS-Arctic Aβ1-42, UAS-Aβarc, [UAS]Aβarc
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

UASt regulatory sequences drive expression of the Tag:SS(nec) secretion signal peptide fused to an Aβ42 peptide carrying the Arctic mutation (amino acid replacement E22G).

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 ( 0 )
 
Disease-implicated variant(s)
 
This allele represents a human variant implicated in disease.

This construct carries the amyloid Aβ42 peptide; variant described relative to the full-length protein and in terms of the Aβ42 peptide.

APP:p.Glu693Gly
Variants Synonym(s)
APP(Aβ42 peptide):p.Glu22Gly
External database links
Comments concerning this variant
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Expression of Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav-C155 significantly reduces the longevity of adult flies: their median survival is significantly decreased compared to controls at both 25[o]C and 29[o]C. It also reduces their locomotor abilities - their mean climbing velocity is lower than in controls and declines more rapidly with age.

The climbing ability of flies expressing Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav.PU declines more significantly with age compared with controls. This individuals are short lived compared to controls.

The brains of flies expressing Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav.PU show an increase in vacuole number compared to controls.

Flies expressing Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav.PU exhibit an impaired circadian activity rhythm in LD (12 house light, 12 hours dark) that becomes more severe with age. The average rhythm strength is also reduced in DD (total darkness).

The morphology and number of Pdf-positive flies is unaffected in the brains of flies expressing Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav.PU.

Expression of Hsap\APPArctic.Scer\UAS.T:SS-nec, induced by RU486 thanks to expression under the control of the Scer\GAL4elav.Switch.PO geneswitch system, is induced by lower doses of RU486 on a holidic (containing 50mM sucrose and 200mM biologically available nitrogen) diet compared to on a sugar-yeast diet. In a dose-response analysis, 25υM RU486 in the holidic medium reproduces both Hsap\APPArctic.Scer\UAS.T:SS-nec expression levels and a similar defect in the flies' ability to perform negative geotaxis at old ages when receiving 200υM RU486 in sugar-yeast food.

Adult- onset expression of Hsap\APPArctic.Scer\UAS.T:SS-nec under the Scer\GAL4elav.Switch.PO driver (using RU486 food supplement to control the time of expression) significantly decreases adult lifespan and climbing abilities compared to controls.

Expression of Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4OK307 induces an age-dependent decline in synaptic vesicle release probability.

Expression of Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4OK307 induces an age-dependent reduction in the density of presynaptic voltage-gated calcium channel clusters.

Expression of Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4OK307 induces an age-dependent increase in synaptic contact length.

Expression of Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav.Switch.PO (in combination with RU486 exposure to activate Gal4 expression) results in climbing defects and reduced lifespan, with increased severity upon longer RU486 exposure, as compared to untreated controls.

Expression of Hsap\APPArctic.Scer\UAS.T:SS-nec under the Scer\GAL4GMR.PF driver results in a rough eye phenotype and a decrease in the adult eye size.

Flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155 display significantly increased survival when cultured on food containing 1000μ YM-F24 (an iron-specific metal chelator).

Expression of Hsap\APPArctic.Scer\UAS.T:SS-nec in the brain under the control of Scer\GAL4elav-C155 results in a drastic reduction in lifespan compared with controls.

Flies expressing Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav.Switch.PO from 2 day post-eclosion onwards (expression induced by feeding flies RU486) have a median lifespan that is shorter than controls by about 50%, and a maximum lifespan that is reduced by about 45%. Response latencies in the tergotrochanteral (TTM) and dorsal longitudinal (DLM) muscles following giant fibre stimulation are similar to controls at day 16, but are significantly increased at day 28. The stability of the TTM response to high frequency stimulation (100, 200 and 250 Hz) is inhibited. Age-related climbing behaviour is enhanced compared to controls, and this phenotype is rescued when the flies are fed lithium in adulthood.

Expression of Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4shot-OK307 significantly accelerates the age-related decline in the flight ability of adult flies and shortens adult lifespan relative to controls. It also hastens the age-related decline in neurotransmission functionality: the success rate of eliciting excitatory junction potentials in the dorsal longitudinal muscle (DLM) fibers in response to brain stimulation is much lower compared to controls and the age-progressive increase in synaptic transmission fatigue rate is increased. Expression of Hsap\APPArctic.Scer\UAS.T:SS-nec also leads to age-progressive depletion of synaptic vesicles, their increased size and heterogeneity, depletion of presynaptic mitochondria (as well as slightly higher frequency of damaged mitochondria) and accumulation of presynaptic vacuoles compared to age-matched controls. The number of axonal mitochondria is also reduced although their mean area is actually increased compared to controls and the rates of both anterograde and retrograde axonal transport in aged (but not young) adult flies is significantly decreased compared to age-matched controls.

The faster rate of age-related decline in neurotransmission along the the DLM pathway is also observed in flies expressing Hsap\APPArctic.Scer\UAS.T:SS-nec under the Scer\GAL4elav.PLu driver, although the decline rate is slower than with the Scer\GAL4shot-OK307 driver.

The metal chelator clioquinol reduces the toxic effects of Hsap\APPArctic.Scer\UAS.T:nec-driven Hsap\APPScer\UAS.T:nec overexpression.

Flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4unspecified have a median survival of about 8 days.

Expression of Hsap\APPArctic.Scer\UAS.T:nec driven by Scer\GAL4elav-C155 results in a rough eye phenotype.

Flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155 show a dramatic decrease in longevity. Treatment with MK-801 markedly prolongs the survival of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.Feeding these flies with azo-dye Congo Red from the time of hatching results in a significant increase in longevity. Congo Red does not lengthen the lifespan of control flies.

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

The short lifespan of adult flies expressing Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav-C155 (cultured at either 25[o]C or 29[o]C) is significantly lengthened by co-expression of NT1Cysknot.Scer\UAS and decreased further by co-expression of NT1Pro.Scer\UAS. Co-expression of NT1fl.Scer\UAS.T:Avic\GFP-EGFP or of NT1GD10831 RNAi has no significant effect on the lifespan of Hsap\APPArctic.Scer\UAS.T:SS-nec expressing flies and neither has the combination with a single copy of NT1unspecified loss of function allele.

The impaired locomotor ability of adult flies expressing Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav-C155 is partially ameliorated by co-expression of either NT1Cysknot.Scer\UAS or NT1fl.Scer\UAS.T:Avic\GFP-EGFP. Co-expression of NT1Pro.Scer\UAS or of NT1GD10831 RNAi has no significant effect on the climbing ability of Hsap\APPArctic.Scer\UAS.T:SS-nec expressing flies and neither has the combination with a single copy of NT1unspecified loss of function allele.

per01 does not enhance the climbing defects seen when Hsap\APPArctic.Scer\UAS.T:SS-nec is expressed under the control of Scer\GAL4elav.PU.

per01 does not further enhance the increase in vacuole number seen when Hsap\APPArctic.Scer\UAS.T:SS-nec is expressed under the control of Scer\GAL4elav.PU.

Expression of Fer1HCHVDRC.cUa in flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155 reduces hatching efficiency.

Expression of Fer2LCHVDRC.cUa in flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155 reduces hatching efficiency.

Flies co-expressing Saur\spaZAβ3.Scer\UAS.T:Hsap\MYC,T:SS-nec with Hsap\APPArctic.Scer\UAS.T:SS-nec via Scer\GAL4elav-C155 live longer than flies expressing Scer\GAL4elav-C155>Hsap\APPArctic.Scer\UAS.T:SS-nec.

Flies co-expressing Saur\spa2.ZAβ3.Scer\UAS.T:Hsap\MYC,T:SS-nec with Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav-C155 live almost as long as wild-type controls.

Co-expression of Saur\spaZ.Scer\UAS.T:Hsap\MYC,T:SS-nec under the control of Scer\GAL4elav-C155 does not affect the viability of flies expressing Hsap\APPArctic.Scer\UAS.T:SS-nec.

Co-expression of Saur\spa2.ZAβ3.Scer\UAS.T:Hsap\MYC,T:SS-nec using Scer\GAL4GMR.PF restores the eye-morphology in flies expressing Hsap\APPArctic.Scer\UAS.T:SS-nec alone.

Expression of sggS9E.Scer\UAS partially suppresses the decrease in median and maximum lifespan seen in flies expressing Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav.Switch.PO from 2 day post-eclosion onwards (expression induced by feeding flies RU486). The climbing behaviour defects are fully rescued.

tauMR22/tauEP3203 suppresses the climbing defects seen in flies expressing Hsap\APPArctic.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav.Switch.PO from 2 day post-eclosion onwards (expression induced by feeding flies RU486). This rescue is further enhanced by feeding the flies lithium in adulthood.

Activation of P{GSV1}811 with Scer\GAL4elav-C155 in flies expressing Hsap\APPArctic.Scer\UAS.T:nec suppresses the decreased survival phenotype of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Activation of P{GSV1}1357 with Scer\GAL4elav-C155 in flies expressing Hsap\APPArctic.Scer\UAS.T:nec suppresses the decreased survival phenotype of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Activation of P{GSV1}1774 with Scer\GAL4elav-C155 in flies expressing Hsap\APPArctic.Scer\UAS.T:nec suppresses the decreased survival phenotype of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of Fer1HCHScer\UAS.cRa suppresses the decreased survival phenotype of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of Fer1HCHScer\UAS.cRa suppresses the decline in locomotor function of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of Fer2LCHScer\UAS.cRa suppresses the decreased survival phenotype of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of Fer2LCHScer\UAS.cRa suppresses the decline in locomotor function of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of CatScer\UAS.cAa suppresses the decreased survival phenotype of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of CatScer\UAS.cAa suppresses the decline in locomotor function of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of Sod2Scer\UAS.cMa suppresses the decreased survival phenotype of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of Sod2Scer\UAS.cMa suppresses the decline in locomotor function of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of SodScer\UAS.cAa enhances the decreased survival phenotype of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of SodScer\UAS.cAa accelerates the decline in locomotor function of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of sniScer\UAS.cBa partially suppresses the decreased survival phenotype of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of GstS1Scer\UAS.P\T.cWa partially suppresses the decreased survival phenotype of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of SoddsRNA.Scer\UAS.cHa suppresses the decreased survival phenotype of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Sodn1 dominantly suppresses the decreased survival phenotype of flies expressing Hsap\APPArctic.Scer\UAS.T:nec under the control of Scer\GAL4elav-C155.

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 (5)
Reported As
Symbol Synonym
Arctic Aβ42
Hsap\APPArctic.Scer\UAS.T:SS-nec
Hsap\APPArctic.Scer\UAS.T:nec
Hsap\APPArctic.UAS.Tag:SS(nec)
Name Synonyms
Secondary FlyBase IDs
    References (22)