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General Information
Symbol
Hsap\APP695.UAS
Species
H. sapiens
Name
FlyBase ID
FBal0095694
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
UAS-APP, P{UAS:APP695}, UAS-APP695, APP695, UAS-AβPP
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

Wild-type Hsap\APP695 is expressed under the control of UASt regulatory sequences.

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
is ameliorated by poloHMS00530
is ameliorated by poloGL00014
is ameliorated by polo1
is ameliorated by PsnB3
Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
 

One copy of Df(2R)Egfr5 exacerbates the neurodegeneration seen in Alzheimer's disease modeled by expression of Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa.

Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Expression of Hsap\APP695.Scer\UAS under the control of Scer\GAL4Appl.G1a results in impaired axonal transport due to axonal blockages in the segmental nerves in third instar larvae.

Flies with Hsap\APP695.Scer\UAS overexpressed by Scer\GAL4Appl.G1a have a severe wing expansion defect and larvae have a significant increase in the number of boutons and branches at the larval neuromuscular junction (NMJ) compared to wild type. There is a significant decrease in the number of type Ib boutons and a significant increase in the number of type Is boutons at the NMJ of larvae with Hsap\APP695.Scer\UAS overexpressed by Scer\GAL4Appl.G1a. Larvae (significantly reduced crawling speed) and adults (significantly reduced climbing speed) with Hsap\APP695.Scer\UAS overexpression by Scer\GAL4Appl.G1a have locomotory defects. Flies with Hsap\APP695.Scer\UAS overexpressed by Scer\GAL4Appl.G1a have a severely shortened lifespan.

When flies with Hsap\APP695.Scer\UAS driven by Scer\GAL4Appl.G1a are reared at 17[o]C and only put at 25[o]C after eclosion, they do not display the wing expansion defect or locomotor defects (tested at 2 days old) that are seen when they are reared at 25[o]C. Climbing ability declines dramatically with aging in flies with adult-specific (reared at 17[o]C, 25[o]C after eclosion) expression of Hsap\APP695.Scer\UAS driven by Scer\GAL4Appl.G1a. Lifespan is reduced in flies with adult-specific (reared at 17[o]C, 29[o]C after eclosion) expression of Hsap\APP695.Scer\UAS driven by Scer\GAL4Appl.G1a.

Male flies with Hsap\APP695.Scer\UAS driven by Scer\GAL4fru-NP0021 show a courtship defect (eliminates courtship preference for younger mates).

Flies with Hsap\APP695.Scer\UAS driven by Scer\GAL4GMR.PU have small rough eyes with reduced pigmentation. Third instar larvae with Hsap\APP695.Scer\UAS driven by Scer\GAL4GMR.PU show abnormal cell cycle re-entry at the eye disc.

3-day-old naive flies expressing Hsap\APP695.Scer\UAS in the central nervous system under the control of Scer\GAL4elav-C155 are unable to distinguish younger females from older females (as wild-type young males can), resembling the phenotype seen in 60-day-old males. In contrast, Hsap\APP695.Scer\UAS-expressing males show no defects in courtship index compared with controls, indicating that Hsap\APP695.Scer\UAS expression does not compromise males' overall courtship ability or courting interest in females. The preferential index (between young and old females) decreases significantly compared with that of controls, suggesting males' discriminating ability is abrogated by pan-neuronal expression of Hsap\APP695.Scer\UAS.

Expression of Hsap\APP695.Scer\UAS in the courtship circuit, under the control of Scer\GAL4fru-NP0021 abolishes the male preference for younger mates but does not affect their total courtship index.

No body wall contraction defects are seen in third instar larvae expressing Hsap\APP695.Scer\UAS under the control of Scer\GAL4elav-C155. Crawling distance and rate are similar to controls.

Expression of Hsap\APP695.Scer\UAS in the nervous system, under the control of the pan-neuronal Scer\GAL4elav-C155 results in elevated cell death in the central nervous system.

Expression of Hsap\APP695.Scer\UAS in the developing eye, under the control of Scer\GAL4GMR.PF induces strong cell death in third-instar larval eye discs and produces rough eyes with reduced size in the adults.

Expression of Hsap\APP695.Scer\UAS in the developing thorax, under the control of Scer\GAL4pnr-MD237 or Scer\GAL4ap-md544 triggers cell death in the thorax region of third-instar larval wing disc and produces a small scutellum phenotype in the adult thorax.

Expression of Hsap\APP695.Scer\UAS along the anterior/posterior compartment boundary in the larval wing disc, under the control of Scer\GAL4ptc-559.1, induces robust cell death and produces a loss of the anterior cross vein in the adult wing.

Expression of Hsap\APP695.Scer\UAS in the developing wing pouch, driven by Scer\GAL4sd-SG29.1 provokes extensive cell death and generates a small wing phenotype in the adults.

Expression of Hsap\APP695.Scer\UAS in the central nervous system, under the control of Scer\GAL4Appl.G1a, results in enhanced cell death and a considerable reduction in locomotory ability.

Expression of Hsap\APP695.Scer\UAS under the control of Scer\GAL4sd-SG29.1 results in strong activation of W and reduced wing pouch size.

Expression of Hsap\APP695.Scer\UAS driven pan-neuronally by Scer\GAL4elav-C155 results in crumpled wings and presence of melanotic masses on the abdomen and proboscis; penetrance is around tenfold reduced compared to what is seen with expression of Hsap\BACE1Scer\UAS.cGa. Compared to genetic controls, Scer\GAL4elav-C155>Hsap\APP695.Scer\UAS young adults have significantly reduced survival. Scer\GAL4elav-C155>Hsap\APP695.Scer\UAS fly brains have similar size mushroom bodies as controls (significantly larger calyx and lobes than is seen with expression of Hsap\BACE1Scer\UAS.cGa). Flies (2-10 and 12-20 days old) with expression of Hsap\APP695.Scer\UAS driven by Scer\GAL4elav-C155 show similar climbing ability to controls.

Expression of Hsap\APP695.Scer\UAS under the control of Scer\GAL4GMR.PU results in accumulation of Aβ peptides, amyloid deposits and age-dependent retinal degeneration.

Flies expressing Hsap\APP695.Scer\UAS under the control of Scer\GAL4Act.PU exhibit premature lethality. Dietary isradipine significantly increases the survival rate in a concentration-dependent manner. No effect is seen when the larvae are fed verapamil.

Ubiquitous expression of Hsap\APP695.Scer\UAS (under the control of Scer\GAL4Act5C.PI) results in a survival rate of about 5% compared to control flies. Raising these flies on food containing increased concentration of HSB-13 results in a significant increase in the survival rate ranging from 65% at 50υM to 44% at 2.5υM compared with equally treated control flies. These survival rates are approximately 10 times higher compared with untreated flies.

Individuals simultaneously heterozygous for Df(2R)Egfr5 and expressing Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4Act.PU are short lived compared to controls.

Flies expressing Hsap\APP695.Scer\UAS in the developing eye under the control of Scer\GAL4GMR.PF leads to no detectable abnormalities.

Expression of Hsap\APP695.Scer\UAS in the eye under the control of Scer\GAL4GMR.PF results in age-dependent photoreceptor degeneration. Amyloid plaques form in the retinae of these flies but this occurs after the onset of neurodegeneration.

Flies expressing Hsap\APP695.Scer\UAS under the control of Scer\GAL4Mz1087.hx have a wing blister phenotype and develop a deformation in one or both wings. Large blisters may occupy more than 50% of the wing surface and in extreme cases the wings appear like balloons. The blisters appear transparent or black, are filled with hemolymph and occur in 5-20% of flies at 25oC. The pattern of wing veins is normal.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Suppressed by
Statement
Reference
NOT suppressed by
Enhancer of
Other
Statement
Reference
Phenotype Manifest In
Enhanced by
Suppressed by
Statement
Reference

Hsap\APP695.UAS, Scer\GAL4Appl.G1a has wing phenotype, suppressible | partially by polo[+]/polo1

NOT suppressed by
Other
Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference

The presence of axonal blockages in the segmental nerves characteristic for third instar larvae expressing Hsap\APP695.Scer\UAS under the control of Scer\GAL4Appl.G1a is rescued by co-expression of Rab5S43N.Scer\UAS.P\T.T:Avic\GFP-YFP, but not Rab5Scer\UAS.P\T.T:Avic\GFP-YFP or Rab5Q88L.Scer\UAS.P\T.T:Avic\GFP-YFP.

Co-expression of poloHMS00530 or poloGL00014 partially suppresses the wing expansion defects, shortened lifespan, locomotion defects (reduced crawling speed in larvae or reduced climbing speed in adults), and increases of bouton and branch number (including decreases in Ib boutons and increases in Is boutons) seen at the larval neuromuscular junction in animals with Hsap\APP695.Scer\UAS driven by Scer\GAL4Appl.G1a.

Co-expression of poloHMS00530 or poloGL00014 partially suppresses the courtship defects in male flies with Hsap\APP695.Scer\UAS driven by Scer\GAL4fru-NP0021.

Co-expression of poloHMS00530 or poloGL00014 partially suppresses the eye development defects in adults and the abnormal cell cycle re-entry at the third instar larval eye disc seen when Hsap\APP695.Scer\UAS is driven by Scer\GAL4GMR.PU.

Adult-specific (reared at 17[o]C, 25[o]C after eclosion) expression of poloHMS00530 or poloGL00014 partially suppresses the decline in climbing ability seen in older flies expressing Hsap\APP695.Scer\UAS driven by Scer\GAL4Appl.G1a during adulthood. Adult-specific (reared at 17[o]C, 29[o]C after eclosion) expression of poloHMS00530 or poloGL00014 partially suppresses shortened lifespan in flies with Hsap\APP695.Scer\UAS driven by Scer\GAL4Appl.G1a during adulthood.

polo1/+ partially suppresses the wing expansion defects, shorter lifespan, locomotion defects (larval and adult), and increases of Is bouton numbers (but does not suppress branch number changes or the decrease of Ib boutons) at the larval neuromuscular junction seen in animals with Hsap\APP695.Scer\UAS driven by Scer\GAL4Appl.G1a.

Co-expression of Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa driven by Scer\GAL4elav.Switch.PO driven by Scer\GAL4elav.Switch.PO (with 200um RU486) results in significant hyperactivity (including nocturnal hyperactivity followed by a rapid decline, the effect is more prominent in male flies, and the effect disappears as flies age); this effect is more striking on a diet with a high carbohydrate to protein ratio (compared to low carbohydrate to protein ratio).

Co-expression of Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa driven by Scer\GAL4elav-C155 results in significant hypoactivity compared to controls, though total activity at night is not significantly altered (it is significantly decreased during the day).

Larvae co-expressing Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4elav-C155 show a significant decrease in third instar larval body wall contractions.

The crawling defects seen when Hsap\BACE1Scer\UAS.cGa is expressed under the control of Scer\GAL4elav-C155 are enhanced upon co-expression of Hsap\APP695.Scer\UAS.

Co-expression of Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4elav-C155 results in structural changes in the synapse of the third instar larval muscle 6 and 7 neuromuscular junctions (NMJs). The overall number of boutons is reduced compared to controls, and this is due to a reduced number of type 1s boutons; the number of 1b boutons is similar to wild type. Both the number of motor neuron branches and the size of muscles 6 and 7 at the NMJ are similar to controls. The density of presynaptic release sites (brp-positive active zones) in motor neurons is also normal, but mitochondrial localisation defects are observed.

Expression of both Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4elav-C155 leads to a subset of flies showing melanotic masses on the ventral proboscis, curled wings, and these flies show a significant and progressive defect in climbing ability beginning at 42 days post-eclosion, a significant decrease in the size of the mushroom body, and a significant decrease in immediate recall memory in a conditioned courtship suppression assay, but do not show a significant decrease in lifespan nor any significant defect in learning ability as compared to controls.

Expression of Psn527.D447A.GMR suppresses the Hsap\APP695.Scer\UAS-induced cell death seen upon expression in the developing wing (under the control of Scer\GAL4ptc-559.1).

A foxoΔ94 mutant background suppresses the Scer\GAL4ptc-559.1-->Hsap\APP695.Scer\UAS induced cell death in the larval wing disc and the loss of anterior cross vein found in these mutants.

Knockdown of foxo through expression of foxoKK108590 suppresses the Scer\GAL4ptc-559.1-->Hsap\APP695.Scer\UAS induced cell death in the larval wing disc and the loss of anterior cross vein found in these mutants.

Knockdown of foxo through expression of foxoKK108590 significantly suppresses the locomotory defects found upon expression of Hsap\APP695.Scer\UAS under the control of Scer\GAL4Appl.G1a.

A foxoΔ94 mutant background suppresses the induced scutellum phenotype found upon expression of Hsap\APP695.Scer\UAS under the control of Scer\GAL4ap-md544 and the Scer\GAL4sd-SG29.1-->Hsap\APP695.Scer\UAS-induced small wing phenotype.

A foxoΔ94 heterozygous background significantly suppresses the locomotory defects found upon expression of Hsap\APP695.Scer\UAS under the control of Scer\GAL4Appl.G1a.

A foxoΔ94 heterozygous background considerably suppresses the reduced wing size (and strong W expression) found in flies expressing Hsap\APP695.Scer\UAS under the control of Scer\GAL4sd-SG29.1.

The pan-neuronal co-expression of Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4elav-C155 leads to a decrease in adult lifespan, as compared to controls.

Co-expression of Hsap\BACE1Scer\UAS.cGa and Hsap\APP695.Scer\UAS under the control of Scer\GAL4elav-C155 results in reduced lifespan compared with controls.

The reduced lifespan of flies co-expressing Hsap\BACE1Scer\UAS.cGa and Hsap\APP695.Scer\UAS under the control of Scer\GAL4elav-C155 is partially suppressed by the co-expression of IdeScer\UAS.cTa.

The reduced lifespan of flies co-expressing Hsap\BACE1Scer\UAS.cGa and Hsap\APP695.Scer\UAS under the control of Scer\GAL4elav-C155 is partially suppressed by the co-expression of Hsap\IDEScer\UAS.cTa.

The ectopic wing vein phenotype induced by co-expressing Hsap\BACE1Scer\UAS.cGa and Hsap\APP695.Scer\UAS under the control of Scer\GAL4Act5C.PI is suppressed by the co-expression of IdeScer\UAS.cTa.

The ectopic wing vein phenotype induced by co-expressing Hsap\BACE1Scer\UAS.cGa and Hsap\APP695.Scer\UAS under the control of Scer\GAL4Act5C.PI is suppressed by the co-expression of Hsap\IDEScer\UAS.cTa.

One copy of Df(2R)Egfr5 enhances the wing vein phenotype seen when Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa are co-expressed under the control of Scer\GAL4Act.PU. The neurodegeneration is also increased, with at least 50% of flies showing clear evidence of neurodegeneration throughout the central brain compared to ~10% in controls and, unlike in controls, a significant fraction show dramatic loss of brain tissue.

Coexpression of Hsap\BACE1Scer\UAS.cGa and Hsap\APP695.Scer\UAS, under the control of Scer\GAL4GMR.PF, leads to a retinal degeneration phenotype that is less severe than that seen when Hsap\APP695.Scer\UAS is expressed alone.

A PsnB3/+ background rescues the age-dependent retinal neurodegeneration phenotype seen when Hsap\APP695.Scer\UAS is expressed under the control of Scer\GAL4GMR.PF. Further, coexpression of PsnL235P.Scer\UAS with Hsap\APP695.Scer\UAS, under the control of Scer\GAL4GMR.PF, enhances the degeneration.

Flies that coexpress Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4Act5C.PI exhibit ectopic wing veins. This phenotype is enhanced in flies that express Psn+14.Scer\UAS in addition to Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4Act5C.PI.

A PsnC4/+ background partially rescues the ectopic wing vein formation and semi-lethality of flies that coexpress Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4Act5C.PI.

Complementation and Rescue Data
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Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
Comments
Comments

Carried in a plasmid and transfected into SL-2 cells with a Scer\GAL4 expression plasmid. The expression and metabolism of Hsap\APP695.Scer\UAS protein in these cells has been studied.

External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (3)
Reported As
Symbol Synonym
Hsap\APP695.Scer\UAS
Hsap\APP695.UAS
Name Synonyms
Secondary FlyBase IDs
    References (20)