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General Information
Symbol
Hsap\APPAβ42.UAS.Tag:SS(nec)
Species
H. sapiens
Name
FlyBase ID
FBal0324202
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
1-42, Aβ42, Aβ42, Aβ1-42, Alz42, UAS-Aβ1-42, UAS-Aβ42, UAS-Aβ42
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 the Aβ1-42 peptide.

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 )
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Adults expressing Hsap\APPAβ42.UAS.Tag:SS(nec) under the control of Scer\GAL4shot-OK307 show a significant decrease in climbing ability, as well as a significant decrease in neurotransmission to DM muscles, as compared to controls.

Expression of Hsap\APPAβ42.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav-C155 results in a significant decrease in lifespan and a significant increase in locomotor defects, as compared to controls.

At ages less than 3 weeks, the latency of evoked dorsal longitudinal flight muscle (DLM) and Tergotrochanter muscle (TTM) excitatory junctional potentials (EJPs) is about 0.8ms in flies expressing one or two copies of Hsap\APP1-42.Scer\UAS.T:SS-nec under the control of Scer\GAL4OK307 (compared to 1.2ms in controls). At ages over 3 weeks, the latencies of evoked DLM and TTM EJPs in flies expressing one or two copies of Hsap\APP1-40.Scer\UAS.T:SS-nec are significantly increased, in a dosage-dependent manner, demonstrating a slowing of neurotransmission in both the TTM and DLP pathways. In some 2xHsap\APP1-42.Scer\UAS.T:SS-nec flies over 3 weeks old, neither DLM nor TTM EJPs are evoked by brain stimulation, demonstrating a loss of neurotransmission. Failure of neurotransmission in the TTM pathway is more frequent than in the DLM pathway, suggesting that the TTM pathway is more susceptible to the intraneuronal accumulation of Hsap\APP, although the TTM pathway is relatively shorter and contains fewer synapses.

Expression of Hsap\APP1-42.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav.PU does not significantly shorten lifespan compared to controls.

Flies expressing Hsap\APP1-42.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav.PU do not show any defects in locomotor rhythm in LD (12 hours light, 12 hours dark). In DD (total darkness) no different from controls is seen at 5 or 35 days, but a substantial difference in rhythm is seen at 50 days.

Adult flies expressing Hsap\APP1-42.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav-C155 show significantly decreased median lifespan relative to controls and rapid age-progressive loss of climbing ability.

Expression of Hsap\APPScer\UAS.T:nec under the control of Scer\GAL4GMR.PF results in age-dependent degeneration of photoreceptor cells.

Expression of Hsap\APPScer\UAS.T:nec under the control of Scer\GAL4elav-C155 results in an age-dependent decrease in locomotor activity compared to controls flies of the same age.

Flies expressing Hsap\APPScer\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 two copies of Hsap\APP1-42.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 (EJP) in the dorsal longitudinal muscle (DLM) fibers in response to brain stimulation is much lower compared to controls and decreases more steeply with the number of stimulations and enhances the age-progressive increase in synaptic transmission fatigue rate. The neurotransmission along the tergotrochanteral muscle pathway is affected to a much lesser degree. Expression of two copies of Hsap\APP1-42.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. Neither the mean area of the mitochondria nor the number of boutons on the neuromuscular junction is significantly changed by expressing either two or just one copy of Hsap\APP1-42.Scer\UAS.T:SS-nec. Expression of just one copy also has much more subtle effect on flight capability of adult flies compared to when two copies are used, and it does not significantly change adult survival rate but it does reduce the DLM EJP success rate.

The metal chelator clioquinol reduces the toxic effects of Scer\GAL4elav-C155-driven Hsap\APPScer\UAS.T:nec overexpression.

Flies expressing Hsap\APPScer\UAS.T:nec under the control of Scer\GAL4unspecified have a median survival of about 24 days.

Expression of Hsap\APPAβ42.Scer\UAS.T:SS-nec under the control of Scer\GAL4GMR.PF leads to a degenerative rough eye phenotype.

Animals expressing Hsap\APPA&bgr1-42.Scer\UAS under the control of Scer\GAL4hs.2sev do not show embryonic lethality.

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

Flies expressing Hsap\APPScer\UAS.T:nec under the control of Scer\GAL4elav-C155 have a shorter lifespan than flies without a transgene. This effect is dependent on the dose of Hsap\APPScer\UAS.T:nec. Treatment with MK-801 markedly prolongs the survival of flies expressing Hsap\APPScer\UAS.T:nec under the control of Scer\GAL4elav-C155. Feeding these flies with azo-dye Congo Red from the time of hatching has no effect on survival.

Flies expressing Hsap\APPScer\UAS.T:nec under the control of Scer\GAL4elav-C155 show accelerated decline in climbing behaviour relative to control flies, becoming immobile by day 10.

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

Co-expression of Hsap\LYZScer\UAS.T:SS-nec suppresses the decrease in lifespan and partially suppresses the locomotor defects seen in flies expressing Hsap\APPAβ42.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav-C155.

Expression of Hsap\APP1-42.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav.PU in a per01 mutant background does not significantly shorten lifespan compared to controls.

per01 enhances the climbing defects seen when Hsap\APP1-42.Scer\UAS.T:SS-nec is expressed under the control of Scer\GAL4elav.PU, but only in younger (5 day old) flies. No effect is seen at 15, 35 and 50 days.

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

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

Co-expression of Saur\spaZAβ3.Scer\UAS.T:Hsap\MYC,T:SS-nec using Scer\GAL4elav-C155 significantly prolongs the lifespan of flies expressing Hsap\APPScer\UAS.T:SS-nec alone.

Co-expression of Saur\spa2.ZAβ3.Scer\UAS.T:Hsap\MYC,T:SS-nec using Scer\GAL4elav-C155 restores the lifespan of flies expressing Hsap\APPScer\UAS.T:SS-nec alone to wild-type levels.

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

Overexpression of GstS1Scer\UAS.P\T.cWa weakly suppresses the decline in locomotor function of flies expressing Hsap\APPScer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Overexpression of sniScer\UAS.cBa does not significantly suppress the decline in locomotor function of flies expressing Hsap\APPScer\UAS.T:nec under the control of Scer\GAL4elav-C155.

Co-expression of HDAC6Scer\UAS.T:SV5\V5 partially suppresses the rough eye phenotype of flies expressing Hsap\APPAβ42.Scer\UAS.T:SS-nec under the control of Scer\GAL4GMR.PF.

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 (9)
Reported As
Symbol Synonym
Hsap\APP1-42.Scer\UAS.T:SS-nec
Hsap\APPAβ1-42.Scer\UAS
Hsap\APPAβ42.Scer\UAS.T:SS-nec
Hsap\APPAβ42.UAS.Tag:SS(nec)
Hsap\APPScer\UAS.T:SS-nec
Hsap\APPScer\UAS.T:nec
Name Synonyms
Secondary FlyBase IDs
  • FBal0248067
  • FBal0197912
References (30)