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General Information
Symbol
Hsap\APPAβ42.UAS.Tag:SS(rPENK)
Species
H. sapiens
Name
FlyBase ID
FBal0324739
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
UAS-Aβ42, UAS-AβH32.12, Aβ42, UAS-Aβ42, UAS-Aβ, UAS-Aβ1-42
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 Hsap\APP Aβ42 peptide, tagged at the N-terminal end with the Tag:SS(rPENK) signal sequence.
Construct: Scer\UAS regulatory sequences drive expression of the "Aβ42" peptide (a cleavage product of Hsap\APP) fused to the T:Rnor\PENK (signal peptide) at the N-terminus.
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 )
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference
Expression of Hsap\APPAβ42.UAS.Tag:SS(rPENK) under the control of Scer\GAL4elav.PU significantly increases spontaneous excitatory post-synaptic current (sEPSC) frequency in the antennal lobe projection neurons of young flies (0-2 days after eclosion) and significantly reduces it in older flies (9-13 days after eclosion), compared to age-matched controls. Expression of Hsap\APPAβ42.UAS.Tag:SS(rPENK) under the control of Scer\GAL4elav.PU also causes significant increases in sEPSC frequency and amplitude, with no differences in waveform, in primary cultures of neurons, isolated at the embryonic stage, after 5 days in vitro, compared to controls; after 9 days in vitro, sEPSC frequency and amplitude are significantly decreased, with significantly faster decay times and shorter half-width times of waveforms, compared to controls. Miniature EPSC (mESPC) frequency, but not amplitude, is significantly higher at 5 days in vitro and significantly lower at 9 days in vitro, with no difference in most kinetic measurements, compared to controls, but the relative contribution of the slow component is significantly increased and that of the fast component is significantly decreased at 9 days in vitro.
Expressing Hsap\APPAβ42.UAS.Tag:SS(rPENK) under the control of Scer\GAL4elav-C155 leads to neurodegeneration, as evident by present of adult brain vacuolization, as compared to controls.
The expression of Hsap\APPAβ42.UAS.Tag:SS(rPENK) under the control of Scer\GAL4elav-C155 leads to a significant decrease in adult locomotor capacity (in negative geotaxis assays) 18 days post eclosion, but not before that, as compared to controls; this expression also leads to the the adult brain showing a significant area loss and some vacuolization, as compared to controls.
Short-term expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK driven by Scer\GAL4elav.Switch.PO (and using RU486 food supplementation to control the time of expression) leads to progressive daytime sleep defects (decrease in overall amount of daytime sleep, average as well as maximum bout length but a slight increase in the number of day sleep bouts, while the sleep consolidation index is concomitantly reduced) and nighttime activity is decreased. However, unrestrained Scer\GAL4elav-C155-driven expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK induces both daytime and nighttime sleep loss already in 2-3 days old adult males and is accompanied by decreased maximum bout length (both day and night) and the daytime bout number is also significantly reduced.
Adult flies expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK under the control of Scer\GAL4GMR.PF display eye morphology defects of varying severity (including size reduction, ommatidial disruption and bristle loss). Expression under the Scer\GAL4elav-C155 driver leads to age-progressive decrease of locomotor (climbing) ability and shorter lifespan.
Adults expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK under the control of Scer\GAL4GMR.PF have eye sizes comparable to controls, but with a rough eye phenotype.
Expression of Hsap\APPAβ42.Scer\UAS under the control of Scer\GAL4elav.PU results in significantly decreased survival rate during development as well as shorter adult life-span of the survivors, it also leads to significantly impaired climbing abilities of the adults compared to controls. Expression of Hsap\APPAβ42.Scer\UAS results in increased levels of cell death and increased number of glial cells in third instar larval brain when expressed under the control of Scer\GAL4elav.PU. It also reduces adult survival rate under oxidative stress conditions compared to controls.
Primary neurons that have been dissociated from late-gastrula stage embryos expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK under the control of Scer\GAL4elav.PU show increased neuronal excitability in 9 day old cultures compared to controls. Mushroom body neuron cultures expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK under the control of Scer\GAL4elav.PU show an increase in the delayed rectifier component at one day, although this is lost after the first day. There is a decease in A-type K[+] current density after 9 days of culture compared with controls and this can be reversed when the neurons are cultured in the presence of the proteosome inhibit MG132. Blocking lysosome function by adding leupeptin to the culture blocks the decrease in A-type currents in a concentration-dependent manner. Adult flies expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK under the control of Scer\GAL4elav.PU do not exhibit any difference in K[+] current density at 3 days, but by 8 days A-type K[+] current density is significantly reduced in mushroom body neurons. Cell capacitance, resting membrane potential and input resistance are unaffected. Blocking proteosome function in adult flies (by co-expressing Prosβ61.B.Scer\UAS and Prosβ21.Scer\UAS and shifting to the permissive temperature at eclosion) prevents the reduction in A-type K[+] current density compared with controls. Larvae expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK pan-neuronally under the control of Scer\GAL4elav.PU exhibit learning defects in odor-association learning assays. Naive preference for fructose and odors and chemotaxis towards known attractants are similar to controls. Flies expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK under the control of Scer\GAL4elav.PU exhibit progressive climbing defects and decreased lifespan compared to controls. Expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK specifically in the mushroom body under the control of Scer\GAL4Tab2-201Y results in loss of mushroom body neurons.
Scer\GAL4elav.PU-mediated expression of Hsap\APPAβ1-42.Scer\UAS.cIa induces brain neurodegeneration, increases caspase activation, and shortens lifespan.
Pan-neuronal expression of Hsap\APPAβ42.Scer\UAS under the control of Scer\GAL4elav.PU reduces lifespan. Flies expressing Hsap\APPAβ42.Scer\UAS in the motoneurons under the control of Scer\GAL4D42 show a similar reduction in lifespan, and this phenotype is made more severe by the addition of an additional motoneuron driver, Scer\GAL4VGlut-OK371. Expression of Hsap\APPAβ42.Scer\UAS under the control of either Scer\GAL4elav.PU, Scer\GAL4D42 or Scer\GAL4D42 and Scer\GAL4VGlut-OK371 has no effect on NMJ morphology or bouton number. Expression of Hsap\APPAβ42.Scer\UAS under the control of Scer\GAL4GMR.PU results in a rough eye phenotype.
Flies expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK under the control of Scer\GAL4GMR.PF show a rough eye phenotype with areas of necrosis.
Expression of Hsap\APPAβ42.Scer\UAS in the compound eye using Scer\GAL4ey.PH causes severe degeneration in eye tissues ranging from loss of bristles, ommatidial holes to severe ommatidial disruption. When Hsap\APPAβ42.Scer\UAS-expressing larvae are grown in medium containing 2-(4' -benzyloxy-phenyl)-3- hydroxy-chromen-4-one, an approximately 70% rescue of the rough eye phenotype is observed. There is also a significant reduction in amyloid plaques in eye imaginal discs of the treated flies compared with controls. The compound also ameliorated the locomotor-deficit resulting from the expression of Hsap\APPAβ42.Scer\UAS under the control of Scer\GAL4elav-C155, and also improves the lifespan of these flies.
Adults expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PU show a defect in climbing ability starting at 15 days of age, and have a reduced lifespan compared to controls. 30 day old adults expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PU show neurodegeneration in both the cortex and neuropil regions of the adult brain. 10 day old adults expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PU show impaired memory performance compared to controls in an olfactory aversive conditioning assay.
Expression of Hsap\APPAβ42.Scer\UAS under the control of Scer\GAL4elav-C155 results in a reduction of median and maximum lifespan by 17 days and 32 days respectively, when compared to controls. Treatment with an aqueous extract from the rhizome of Gastrodia elata (GE) (1-5mg/g) improves survival. Addition of 1mg/g GE extract increases median and maximum lifespan by 4 days. A 5mg/g GE extract increases the median and maximum lifespan by 7 days. Expression of Hsap\APPAβ42.Scer\UAS under the control of Scer\GAL4elav-C155 significantly impairs locomotion from day 9 onwards. Treatment with an aqueous extract from the rhizome of Gastrodia elata (GE) improves locomotion from days 12-23.
Flies expressing Scer\GAL4GMR.PF>Hsap\APPAβ42.Scer\UAS show mild and severe eye degeneration phenotypes when cultured in normal food. The severity of eye degeneration is enhanced in Cu treated flies as compared with untreated flies, while the percentage of flies showing severe defect is unaltered. Treatment of flies with compound L (2,6-Pyridinedicarboxylic acid, 2,6-bis(2-((4-carboxyphenyl) methylene) hydrazide)) ameliorates the eye neurodegeneration phenotypes.
Expression of Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PLu results in vacuolisation in both the cortex and neuropil region of 20 day old flies. Flies expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PLu begin to display locomotor defects at between 20 and 25 days old. Lifespan is also shortened compared to controls. When mutant flies are subjected to olfactory aversive conditioning they exhibit memory defects from 5 days old.
No memory loss is detectable in 5-day-old adult flies expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PU but 10-day-old flies display significant loss of memory in the aversive olfactory memory assay.
Brain neurons from both young (1 day old) and older (16 day old) flies expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK under the control of Scer\GAL4Gad1.PU exhibit numerous large autophagy-lysosomal vesicles, and the older flies occasionally show necrotic-like intraneuronal degeneration and show significant neuron loss, as compared to controls. Expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK under the control of Scer\GAL4elav.Switch.PO during either larval stage only, the entire adult stage only, the first 15 days of adulthood or during days 21-36 (temporally controlled via RU486 feeding) leads to a significant decrease in maximum lifespan, as compared to non-RU486-treated controls.
Evoked excitatory junction current in muscle 12 synapses in larval body-wall segments 4 an 5 are reduced upon presynaptic expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK, under the control of Scer\GAL4elav-C155. This finding is true at a range of Ca[2+] concentrations. Post-synaptic expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK, under the control of Scer\GAL4G7, significantly increases the excitatory junction current across larval muscle synapses. Expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK in both neuron and muscle cells, under the control of Scer\GAL4arm.PS reduces EJC amplitude. The frequency of mEJCs is significantly decreased upon neuronal expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK under the control of Scer\GAL4elav-C155. Both frequency and amplitude are unaffected by muscle expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK (under the control of Scer\GAL4G7). The evoked release of synaptic vesicles is reduced in larvae with neuronal expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK, under the control of Scer\GAL4elav-C155 and increased upon expression in the muscle, under the control of Scer\GAL4G7. Long-term depression in EJCs at the neuromuscular junction is significantly enhanced by postsynaptic expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK, under the control of Scer\GAL4G7 or Scer\GAL4C57. Long-term depression in EJCs at the neuromuscular junction is not affected by neuronal expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK, under the control of Scer\GAL4elav-C155. Oligomerization inhibitor 1,2-naphthoquinone reverses the reduced EJCs seen upon expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK, under the control of Scer\GAL4elav-C155, but has no effect on synaptic transmission enhancement due to muscle expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK. Conversely, fibrillization inhibitor, apigenin, neutralises the enhanced EJCs caused by expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK in muscle but does not reverse the synaptic transmission depressed by neuronal expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK. Furthermore, apigenin completely suppresses enhanced EJC long-term depression in larvae expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK in the muscle, under the control of Scer\GAL4G7, while 1,2-naphthoquinone has no effect.
Expression of Hsap\APPAβ1-42.Scer\UAS.cIa in neurons driven by Scer\GAL4elav-C155 induces mitochondrial mislocalisation. There are more mitochondria in the cell bodies of neurons, while there appears to be fewer of them in axons and dendrites. A similar phenotype is observed using Scer\GAL4Cha.7.4 as a driver. Flies expressing Hsap\APPAβ1-42.Scer\UAS.cIa in neurons driven by Scer\GAL4elav-C155 display age-dependent progressive locomotor dysfunction starting from 14 days after eclosion. Flies expressing Hsap\APPAβ1-42.Scer\UAS.cIa in cholinergic neurons driven by Scer\GAL4Cha.7.4 display age-dependent progressive locomotor dysfunction by 17 days after eclosion.
Expression of Hsap\APPAβ42.Scer\UAS under the control of Scer\GAL4ChAT.7.4 results in a significant reduction in lifespan, and progressive climbing defects, as compared to controls. Many neurons in these flies exhibit increased size, an increased volume of cytoplasm, subcellular damage to plasma membranes, nuclear membranes, organelles such as mitochondria, or small trafficking vesicles, correlated with the progressive accumulation of large autophagic vesicles at a post-lysosomal fusion stage. Neuropil areas also exhibit some damage as compared to controls.
Expression of Hsap\APPAβ1-42.Scer\UAS.cIa driven by Scer\GAL4elav-C155 results in neurodegeneration, locomotor dysfunction and decreased adult lifespan. 1 hour memory of 5 day old mutant flies is indistinguishable from controls, however, memory defects do manifest in 10 day old flies. Scer\GAL4elav-C155- or Scer\GAL4ey-OK107-driven expression of Hsap\APPAβ1-42.Scer\UAS.cIa results in neuropil degeneration in flies 79 days after eclosion. Calyxes in the adult mushroom body expressing Scer\GAL4ey-OK107-driven Hsap\APPAβ1-42.Scer\UAS.cIa start to degenerate 79 days after eclosion.
Expression of Hsap\APPAβ42.Scer\UAS in the eye under the control of Scer\GAL4GMR.PF results in a rough-eye phenotype.
Expression of Hsap\APPAβ42.Scer\UAS using Scer\GAL4elav-C155 reduces life span. Only approximately 50% of these flies are alive at 20 days, compared to approximately 95% of controls. By 28 days, all Hsap\APPAβ42.Scer\UAS, Scer\GAL4elav-C155 flies are dead whereas 70-90% of control flies are still alive. Starting around days 7-9, Hsap\APPAβ42.Scer\UAS, Scer\GAL4elav-C155 flies show slower locomotion and altered tapping reflex and grooming routines.
2- to 3-day old adults expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK under the control of Scer\GAL4elav-C155 do not show any significant defects in a Pavlovian olfactory learning assay. The flies being to show a subtle, but statistically significant, learning defect at 6-7 days old, and the decline is most obvious in 14-15 day old flies. Defects are greater in male flies than in female flies (consistent with higher expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK in the male flies). Odour avoidance (to methylcyclohexanol) and electric shock reactivity is normal in 14- to 15-day old flies expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK under the control of Scer\GAL4elav-C155. Adults expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK under the control of Scer\GAL4elav-C155 start to show locomotor dysfunction after 3 weeks of age; the climbing ability of these flies in response to light tapping begins to decline significantly 20 days after eclosion and older flies stay at the bottom of the vial and cannot climb up the wall. The lifespan of flies expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK under the control of Scer\GAL4elav-C155 is much shorter than that of control flies. Aged adults expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK under the control of Scer\GAL4elav-C155 show extensive neurodegeneration; 45 day old flies have severe neuronal loss, as seen by the number of vacuoles in the Kenyon cell layer. The majority of dying neurons in the Kenyon cell layer show typical features of necrotic cell death; digested cytoplasm with swollen mitochondria, whereas nuclei are relatively intact. 3- and 14-day old adults do not show detectable abnormalities in the brain, but a small amount of cell loss starts to be apparent in 30-day old flies. Expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK under the control of Scer\GAL4OK107 also results in neurodegeneration.
External Data
Interactions
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Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
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Reference
The decreased locomotion in 18 days old adults induced by the expression of Hsap\APPAβ42.UAS.Tag:SS(rPENK) under the control of Scer\GAL4elav-C155 is enhanced either by the co-expression of HpdKK105686 or by heterozygosity for Df(3L)BSC839, Df(3L)BSC368, Df(3L)BSC797, Df(3L)BSC800, Df(3R)FDD-0317950, CG17249A362 or HpdMI12465, is suppressed by heterozygosity for Df(3R)Exel6202, and is not affected by heterozygosity for Df(3R)ED6280; the observed adult brain loss and vacuolization, however, are not affected by the co-expression of HpdKK105686 or by heterozygosity for HpdMI12465.
The sleep loss and fragmentation induced by Scer\GAL4elav-C155-driven expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK are rescued by co-expression of either fabphs.PG or Mmus\Fabp7hs.PG.
The small eye size observed upon expression of Hsap\MAPTScer\UAS.cWa driven by Scer\GAL4GMR.PF is enhanced by the co-expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK alone; this enhancement is not suppressed by also co-expressing sgg[GL00277]. Co-expression of Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK and Hsap\MAPTS2A.Scer\UAS.0N4R under the control of Scer\GAL4GMR.PF results in eye sizes comparable to controls. Adults co-expressing Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK and sggGL00277 under the control of Scer\GAL4GMR.PF have eye sizes comparable to controls.
The increased mortality during development as well as the reduced climbing abilities of adults characteristic for flies expressing Hsap\APPAβ42.Scer\UAS under the control of Scer\GAL4elav.PU are aggravated further by co-expression of sraEY07182. The decreased adult life-span observed both in flies expressing sraEY07182 or Hsap\APPAβ42.Scer\UAS under the control of Scer\GAL4elav.PU is reduced further when the two transgenes are co-expressed. The high level of cell death in third instar larval brain as well as the reduced adult survival rate under oxidative stress conditions seen in flies expressing either Hsap\APPAβ42.Scer\UAS or sraEY07182 under the control of Scer\GAL4elav.PU are aggravated further when the two transgenes are expressed simultaneously. The increased number of glial cells in third instar larval brain observed in larvae expressing either Hsap\APPAβ42.Scer\UAS, sraEY07182 or CanA1JF01871 under the control of Scer\GAL4elav.PU does not increase further when either Hsap\APPAβ42.Scer\UAS and sraEY07182 or Hsap\APPAβ42.Scer\UAS and CanA1JF01871 are co-expressed. The increased mortality during development characteristic for flies expressing either Hsap\APPAβ42.Scer\UAS or under the control of CanA1JF01871 is dramatically increased if both Hsap\APPAβ42.Scer\UAS and CanA1JF01871 are expressed simultaneously.
Expression of ShalScer\UAS.cPa suppresses the increased excitability seen in primary neurons that have been dissociated from late-gastrula stage embryos expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PU. The average current required to induce action potential firing is similar to controls. Expression of ShalScer\UAS.cPa suppresses the learning defects seen in larvae expressing Hsap\APPAβ1-42.Scer\UAS.cIa pan-neuronally under the control of Scer\GAL4elav.PU. Expression of ShalScer\UAS.cPa suppresses the climbing defects and mushroom body neuron loss seen in flies expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PU to near wild type levels. Expression of ShalScer\UAS.cPa suppresses the mushroom body neuron loss seen in flies expressing Hsap\APPAβ1-42.Scer\UAS.cIa specifically in the mushroom body under the control of Scer\GAL4Tab2-201Y. Expression of ShalScer\UAS.cPa slightly but significantly suppresses the reduction in lifespan seen when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed under the control of Scer\GAL4elav.PU. Expression of ShScer\UAS.cJa does not suppress the learning defects seen in larvae expressing Hsap\APPAβ1-42.Scer\UAS.cIa pan-neuronally under the control of Scer\GAL4elav.PU. Expression of ShScer\UAS.cJa does suppress the progressive climbing defects seen in adult flies expressing Hsap\APPAβ1-42.Scer\UAS.cIa pan-neuronally under the control of Scer\GAL4elav.PU. Expression of ShScer\UAS.cJa suppresses the mushroom body neuron cell loss seen in adult flies expressing Hsap\APPAβ1-42.Scer\UAS.cIa pan-neuronally under the control of Scer\GAL4elav.PU at 25 days, but not at 40 days. Expression of ShScer\UAS.cJa does not suppress the reduction in lifespan seen when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed under the control of Scer\GAL4elav.PU. Expression of ShEKO.Scer\UAS.T:Avic\GFP-GL does not suppress the learning defects seen in larvae expressing Hsap\APPAβ1-42.Scer\UAS.cIa pan-neuronally under the control of Scer\GAL4elav.PU. The progressive climbing defects seen in adult flies are also not suppressed. Expression of ShEKO.Scer\UAS.T:Avic\GFP-GL does not suppress the mushroom body neuron loss seen in flies expressing Hsap\APPAβ1-42.Scer\UAS.cIa specifically in the mushroom body under the control of Scer\GAL4Tab2-201Y. Expression of ShEKO.Scer\UAS.T:Avic\GFP-GL does not suppress the reduction in lifespan seen when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed under the control of Scer\GAL4elav.PU.
Expression of fz2Scer\UAS.T:Avic\GFP does not suppress the reduction in lifespan seen when Hsap\APPAβ42.Scer\UAS is expressed in motoneurons under the control of Scer\GAL4D42. Expression of fz2Scer\UAS.T:Avic\GFP does not suppress the reduction in lifespan seen when Hsap\APPAβ42.Scer\UAS is expressed pan-neuronally under the control of Scer\GAL4elav.PU. Expression of sggGD1331 does not suppress the reduction in lifespan seen when Hsap\APPAβ42.Scer\UAS is expressed in motoneurons under the control of Scer\GAL4D42. Expression of sggGD1331 does not suppress the reduction in lifespan seen when Hsap\APPAβ42.Scer\UAS is expressed pan-neuronally under the control of Scer\GAL4elav.PU. Expression of sggGD1331 does not suppress the rough eye phenotype seen when Hsap\APPAβ42.Scer\UAS is expressed pan-neuronally under the control of Scer\GAL4GMR.PU. Expression of GαoGTP.Scer\UAS does not suppress the rough eye phenotype seen when Hsap\APPAβ42.Scer\UAS is expressed pan-neuronally under the control of Scer\GAL4GMR.PU.
Co-expression of Ctr1CdsRNA.Scer\UAS.cLa partially suppresses the climbing defects and reduced lifespan of adults expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PU. The double mutant flies show defects in climbing ability starting at 30 days of age and show a 32.4% increase in median lifespan compared to Hsap\APPAβ1-42.Scer\UAS.cIa, Scer\GAL4elav.PU single mutant flies. Co-expression of Ctr1CdsRNA.Scer\UAS.cLa significantly decreases the neurodegeneration seen in the brains of 30 day old adults expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PU. Co-expression of Ctr1CdsRNA.Scer\UAS.cLa does not rescue the impaired memory performance of 10 day old adults expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PU in an olfactory aversive conditioning assay. Co-expression of Ctr1CdsRNA.Scer\UAS.cLa significantly increases the resistance of flies expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PU to paraquat. Co-expression of Ctr1BNIG.7459R ameliorates the climbing defects and reduced lifespan of adults expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PU. Co-expression of ATP7EY07895 ameliorates the climbing defects and reduced lifespan of adults expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PU.
Expression of ZIP1Scer\UAS.cLa enhances the brain vacuolisation phenotype seen in 20 day old flies when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed under the control of Scer\GAL4elav.PLu. Expression of ZIP1dsRNA.Scer\UAS suppresses the brain vacuolisation phenotype seen in 20 day old flies when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed under the control of Scer\GAL4elav.PLu. Expression of ZIP1GD1830 suppresses the brain vacuolisation phenotype seen in 20 day old flies when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed under the control of Scer\GAL4elav.PLu. Expression of ZIP1Scer\UAS.cLa enhances the locomotor defects seen when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed under the control of Scer\GAL4elav.PLu. Flies begin to display climbing defects at around 15 days after eclosion, as opposed to 20-25 days when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed alone. Expression of ZIP1dsRNA.Scer\UAS suppresses the locomotor defects seen when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed under the control of Scer\GAL4elav.PLu. Flies begin to display climbing defects at around 30 days after eclosion, as opposed to 20-25 days when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed alone. Expression of ZIP1GD1830 suppresses the locomotor defects seen when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed under the control of Scer\GAL4elav.PLu. Flies do not begin to display climbing defects until around 30 days after eclosion, rather than 20-25 days as is seen when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed alone. Expression of ZIP1Scer\UAS.cLa enhances the reduction in lifespan seen when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed under the control of Scer\GAL4elav.PLu. Median lifespan is reduced by 12.5% and 22.2% at 25[o]C and 29[o]C respectively. Expression of ZIP1dsRNA.Scer\UAS suppresses the reduced lifespan seen when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed under the control of Scer\GAL4elav.PLu. An increase in the median lifespan is seen at both 25[o]C and 29[o]C. Expression of ZIP1Scer\UAS.cLa partially suppresses the memory loss seen in 5 day old flies when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed under the control of Scer\GAL4elav.PLu. Expression of ZIP1dsRNA.Scer\UAS partially suppresses the memory loss seen in 5 day old flies when Hsap\APPAβ1-42.Scer\UAS.cIa is expressed under the control of Scer\GAL4elav.PLu.
The age-progressive memory induced by expression of Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav.PU is enhanced by co-expression of either EgfrScer\UAS.cUa or InRScer\UAS.cUa : the memory defect are detectable even in young 5-day-old flies that perform normally in the aversive olfactory memory assay when expressing Hsap\APPAβ1-42.Scer\UAS.cIa alone.
MiroSd32 heterozygosity enhances the locomotor defects in flies induced by Scer\GAL4elav-C155-driven overexpression of Hsap\APPAβ1-42.Scer\UAS.cIa. Flies overexpressing Hsap\APPAβ1-42.Scer\UAS.cIa driven by Scer\GAL4Cha.7.4 in a rut1 mutant background display age-dependent progressive locomotor dysfunction significantly earlier than Hsap\APPAβ1-42.Scer\UAS.cIa-overexpressing flies without rut1 in the genetic background. dnc1 suppresses the locomotor defects in flies induced by Scer\GAL4Cha.7.4-driven overexpression of Hsap\APPAβ1-42.Scer\UAS.cIa. Co-expression of Pka-C1GD1276 enhances the locomotor defects in flies induced by Scer\GAL4elav-C155-driven overexpression of Hsap\APPAβ1-42.Scer\UAS.cIa. Co-expression of Pka-R2EP2162 enhances the locomotor defects in flies induced by Scer\GAL4elav-C155-driven overexpression of Hsap\APPAβ1-42.Scer\UAS.cIa. Co-expression of Pka-R2EY11550 enhances the locomotor defects in flies induced by Scer\GAL4elav-C155-driven overexpression of Hsap\APPAβ1-42.Scer\UAS.cIa. Co-expression of Pka-R2GD15709 suppresses the locomotor defects in flies induced by Scer\GAL4elav-C155-driven overexpression of Hsap\APPAβ1-42.Scer\UAS.cIa.
Atg1Δ3D/+ leads to partial suppression of the lifespan reduction seen in flies expressing Hsap\APPAβ42.Scer\UAS under the control of Scer\GAL4ChAT.7.4. Co-expression of Atg5dsRNA.Scer\UAS leads to partial suppression of the lifespan reduction seen in flies expressing Hsap\APPAβ42.Scer\UAS under the control of Scer\GAL4ChAT.7.4.
Expression of Hsap\MMEScer\UAS.cIa dramatically suppresses the neuron loss seen in the brains of 28 day old flies expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav-C155. Fewer vacuoles are seen in the cell body regions. The reduction in lifespan is not rescued. Expression of Hsap\MMEmut.Scer\UAS does not suppress the neuron loss seen in the brains of 28 day old flies expressing Hsap\APPAβ1-42.Scer\UAS.cIa under the control of Scer\GAL4elav-C155. The reduction in lifespan is not rescued.
Expression of Hsap\APPAβ42.Scer\UAS and Hsap\MAPTScer\UAS.cWa in the eye under the control of Scer\GAL4GMR.PF results in a severe rough-eye phenotype, enhanced compared to over-expression of each transgene alone. Expression of Hsap\APPAβ42.Scer\UAS in flies expressing Hsap\MAPTE14.Scer\UAS under the control of Scer\GAL4GMR.PF does not enhance the rough-eye phenotype. Expression of Hsap\APPAβ42.Scer\UAS in flies expressing Hsap\MAPTAP.Scer\UAS under the control of Scer\GAL4GMR.PF does not enhance the rough-eye phenotype.
Co-expression of Nep2EP3549, but not IdeEP3099, suppresses the reduced life span seen in Hsap\APPAβ42.Scer\UAS, Scer\GAL4elav-C155 flies.
Complementation and Rescue Data
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Synonyms and Secondary IDs (5)
Reported As
Symbol Synonym
Hsap\APPAβ1-42.Scer\UAS.cIa
Hsap\APPAβ42.Scer\UAS.T:Rnor\PENK
Hsap\APPAβ42.Scer\UAS.T:Rnor\SS-PENK
Hsap\APPAβ42.Scer\UAS
Hsap\APPAβ42.UAS.Tag:SS(rPENK)
Name Synonyms
Secondary FlyBase IDs
  • FBal0183231
  • FBal0246258
  • FBal0243228
References (34)