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General Information
Symbol
Hsap\APP695.UAS.Tag:MYC
Species
H. sapiens
Name
FlyBase ID
FBal0138483
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
UAS-APP, UAS-APP695-N-myc
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

Similar to P{UAS-APP.695}, though tagged with Tag:MYC at the N-terminal end.

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

The expression of Hsap\APP695.UAS.Tag:MYC under the control of Scer\GAL4elav-C155 leads to third instar larvae presenting severely decreased olfactory learning and memory, despite of apparently normal naive olfactory and gustatory responses, as compared to controls. Expression under the control of Scer\GAL4ey-OK107 leads to a significant decrease in the size of the larval mushroom body size, but not of the (7 days old) adult mushroom body or of the overall larval or (7 days old) adult brain, as compared to controls.

Expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4GMR.PU results in a mild rough-eye phenotype.

Expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav.PU results in significantly decreased survival rate during development but adult survival rate under oxidative stress conditions is not affected compared to controls.

Flies expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4ey-OK107 exhibit abnormal morphology of the mushroom body, with both the alpha- and beta-lobes being significantly thinner and shorter as compared to controls. These flies also show a loss of mushroom body neuroadaptive response to environmental enrichment in the first 5 days of adulthood, in contrast to wild type flies, which exhibit an increase in mushroom body size when housed with other flies during the first 5 days of adulthood, versus those kept in isolation.

Males expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4Gr33a-GAL4 show no difference in courtship intensity as compared with controls, but lose preference for younger females, instead showing no significant preference for either younger or older females; and also display loss of neurons in labella and foreleg tarsi.

Expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4c739 results in severe short term memory defects in flies throughout adulthood in a pavlovian olfactory conditioning context. These flies also show memory acquisition and retention defects in a 10-trial spaced training protocol, with severely reduced performance both immediately and 24 h after training. Aged (30-33 day old and 45 day old) flies fed the calcineurin inhibitors cyclosporin A or FK506 exhibited significant rescue of short term memory defects as compared to age-matched controls.

Expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4c739 does not affect gross morphology of the mushroom body.

Expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of transient activation of Scer\GAL4Mef2.247.Switch results in short term memory defects in both young (2-4 day old) and old (30-33 day old) adult flies in a pavlovian olfactory conditioning context.

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

Scer\GAL4ey-OK107>Hsap\APP695.Scer\UAS.T:Hsap\MYC male flies do not show normal learning in a conditioned courtship suppression assay (placed with a mated female for 60 minutes), with no significant drop (unlike wild type) in courtship index when comparing the first 10 minutes to the final 10 minutes. Two minutes after training, flies are placed with a virgin female and courtship is assessed for 10 minutes: trained controls show significantly reduced courtship index when compared to sham (untrained males), whereas Scer\GAL4ey-OK107>Hsap\APP695.Scer\UAS.T:Hsap\MYC males show no significant drop (immediate-recall memory defect).

Third instar larvae expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav-C155 are significantly less mobile and perform significantly fewer full body peristaltic contractions in a locomotor assay compared to controls. The time taken for the larvae to right themselves after being turned ventral side up is also significantly longer than normal.

Larvae expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav-C155 show abnormal aggregations of vesicles on motor neurons extending from the central nervous system.

Expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC driven by Scer\GAL4GMR.PU causes age-dependent degeneration (similar to controls at day 1, with a significant percentage of the area of the retina lost and appearance of vacuoles at day 15 and even more so at day 45) of photoreceptor neurons; mutant flies also show progressive loss of phototaxis (significant decrease in the percentage of phototactic flies at day 15 and 30 but not day 1 compared to controls).

Expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC driven by Scer\GAL4GMR.PU causes the formation of Hsap\APP aggregates in photoreceptor axons (axonal transport abnormalities, detected at day 45 in adults).

Expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC driven by Scer\GAL4elav.PU causes accumulation of synaptic vesicles in axons (significant increase in co-localized Syt1 Hsap\APP aggregates, and the percentage and speed of Syt1 vesicles or mitochondria moving in retrograde or anterograde directions is significantly reduced) at the neuromuscular junction of third instar larvae; larvae also show significant locomotor impairments. Expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC driven by Scer\GAL4elav.PU does not affect distribution or density of mitochondria, or microtubule integrity, at the third instar larval NMJ.

Scer\GAL4elav.PU>Hsap\APP695.Scer\UAS.T:Hsap\MYC larvae show significant increases in bouton number (synapse proliferation) and satellite boutons at the NMJ.

Expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4P2.4.Pdf has no significant effect on the axonal pattern of the s-LNv neurons either in third instar larval or in adult brains but it leads to disrupted sleep pattern in adult flies compared to controls: nighttime sleep is significantly reduced with concomitant increase in daytime sleep.

Ubiquitous induction of Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4337Y results in 60% lethality that occurs in the pupal stage, with the remaining 40% of progeny surviving only 2-5 days after eclosion.

Moderate levels of apoptotic cell death are observed in third instar larval brains expressing Scer\GAL4179Y>Hsap\APP695.Scer\UAS.T:Hsap\MYC.

External Data
Interactions
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Phenotypic Class
Enhanced by
NOT Enhanced by
Suppressed by
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NOT suppressed by
Enhancer of
NOT Enhancer of
Suppressor of
NOT Suppressor of
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Phenotype Manifest In
Enhanced by
NOT Enhanced by
Suppressed by
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Enhancer of
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Additional Comments
Genetic Interactions
Statement
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Xenogenetic Interactions
Statement
Reference

The decreased olfactory learning and memory exhibited by third instar larvae upon the expression of Hsap\APP695.UAS.Tag:MYC under the control of Scer\GAL4elav-C155 is partially suppressed by the co-expression of Tip60UAS.cPa. The smaller larval mushroom body induced by the expression of Hsap\APP695.UAS.Tag:MYC under the control of Scer\GAL4ey-OK107 is also partially suppressed by the co-expression of Tip60UAS.cPa.

The increased mortality during development characteristic for adult flies expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav.PU is improved by co-expression of sraEY07182.

Co-expression of Tip60Scer\UAS.cLa suppresses the mushroom body morphological defects, observed in flies expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4ey-OK107. The mushroom body neuroadaptive response to environmental enrichment is also restored in these flies.

Co-expression of Tip60E431Q.Scer\UAS exacerbates axonal defects in all three mushroom body lobes, resulting in a lack of structural consistency of the mushroom body in flies expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4ey-OK107.

The younger female preference defect of males expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4Gr33a-GAL4 is significantly rescued in the presence of the foxoΔ94/+ mutation.

Co-expression of CanBJF02616 significantly rescues the short term memory defects of flies expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4c739.

Introducing the sgg1 mutation to flies expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4c739 does not result in any rescue of short term memory defects.

Co-expression of Pka-C1Scer\UAS.T:Zzzz\FLAG significantly rescues the short term memory defects of flies expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4c739.

Co-expression of sraScer\UAS.cCa fully rescues the short term memory defects of flies expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of transient activation of Scer\GAL4Mef2.247.Switch.

Co-expression of sraScer\UAS.cCa and Hsap\APP695.Scer\UAS.T:Hsap\MYC (under the control of Scer\GAL4c739) fully rescues the short term memory defect in young (< 10 day old) adult flies, but not in older (> 30 day old) flies, as compared to flies with either construct alone, and does not affect gross morphology of the mushroom body.

Co-expression of sraScer\UAS.cCa partially rescues performance after 10-trial spaced training in flies with Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4c739.

Co-expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC and sraJF02557 (under the control of Scer\GAL4c739) results in a similar performance index in short term memory assays as expression of either construct alone.

Larvae co-expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC and Hsap\BACE1Scer\UAS.Exel 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.Exel is expressed under the control of Scer\GAL4elav-C155 are enhanced upon co-expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC.

The body wall contraction and crawling phenotypes seen in flies co-expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC and Hsap\BACE1Scer\UAS.Exel under the control of Scer\GAL4elav-C155 on standard food are partially rescued when the flies are raised on food containing the γ-secretase inhibitor L-685,458.

Co-expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC and Hsap\BACE1Scer\UAS.Exel under the control of Scer\GAL4elav-C155 results in structural changes in the synapse of the muscle 6 and 7 NMJ. These structural changes are rescued when the flies are raised on the γ-secretase inhibitor L-685,458. The overall number of boutons is reduced compared to controls, with reductions in the numbers of both 1b and 1s boutons. The 1s bouton phenotype is significantly rescued by L-685,458, and the 1b phenotype is partially rescued. The total area of motor neuron innervation in flies expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC and Hsap\BACE1Scer\UAS.Exel is similar to controls, but a significant reduction is seen in the amount of motor neuron branching, as well as the size of muscles 6 and 7 at the NMJ. Feeding the larvae L-685,458 suppresses the branching defect, but has no effect on the reduction in muscle size. The density of presynaptic release sites (brp-positive active zones) is normal, both on standard food or L-685,458. Mitochondrial localisation defects are seen in motor neurons and this is also rescued by L-685,458.

Co-expression of Tip60Scer\UAS.cLa (but not Tip60E431Q.Scer\UAS) suppresses learning and memory defects in Scer\GAL4ey-OK107>Hsap\APP695.Scer\UAS.T:Hsap\MYC males.

Expression of DmtnScer\UAS.cHa suppresses the predominantly male semi-lethality and wing expansion defects seen when Hsap\APP695.Scer\UAS.T:Hsap\MYC is expressed in neurons under the control of Scer\GAL4elav-C155.

Expression of DmtnGD2834 partially suppresses the predominantly male semi-lethality seen when Hsap\APP695.Scer\UAS.T:Hsap\MYC is expressed in neurons under the control of Scer\GAL4elav-C155 (co-expressed with Dcr-2Scer\UAS.cDa). The wing expansion defects are enhanced compared to expression of DmtnGD2834 alone.

Larvae co-expressing both Tip60E431Q.Scer\UAS and Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav-C155 show a synergistic enhancement of the locomotor defects that are seen in larvae expressing either Tip60E431Q.Scer\UAS or Hsap\APP695.Scer\UAS.T:Hsap\MYC alone. In addition, the formation of axonal vesicle accumulations is exacerbated in the double mutants.

Co-expression of Tip60Scer\UAS.cLa partially suppresses the locomotor defects and vesicle accumulation on motor axons that is seen in third instar larvae expressing Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav-C155.

Co-expression of sraScer\UAS.T:Ivir\HA1 significantly delays the onset of age-dependent retinal degeneration and suppresses age-dependent phototaxis defects in flies with expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC driven by Scer\GAL4GMR.PU. sra1 significantly enhances age-dependent retinal degeneration and phototaxis defects in flies with expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC driven by Scer\GAL4GMR.PU. Co-expression of sraScer\UAS.T:Ivir\HA1 suppresses formation of Hsap\APP aggregates in photoreceptor axons in flies with Hsap\APP695.Scer\UAS.T:Hsap\MYC driven by Scer\GAL4GMR.PU, likely alleviating blocked transport to synaptic terminals in the medulla.

sra1 slightly (but not significantly) increases synaptic vesicle accumulation (aggregates) seen in axons at the neuromuscular junction (and does not enhance locomotor defects) in third instar larvae with expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC driven by Scer\GAL4elav.PU. Co-expression of sraJF02557 significantly enhances aggregate formation in axons at the NMJ (but does not enhance locomotor defects) of Scer\GAL4elav.PU>Hsap\APP695.Scer\UAS.T:Hsap\MYC larvae; Syt1 anterograde and retrograde transport and speed is also reduced in larval motor axons. Co-expression of sraScer\UAS.T:Ivir\HA1 significantly partially suppresses aggregate formation in axons and locomotion defects at the Scer\GAL4elav.PU>Hsap\APP695.Scer\UAS.T:Hsap\MYC third instar larval NMJ; Syt1 vesicle or mitochondrial anterograde and retrograde transport is also facilitated in larval motor axons.

Co-expression of sraScer\UAS.T:Ivir\HA1 significantly suppresses the increases in bouton number (synapse proliferation), but not satellite bouton number at the NMJ in Scer\GAL4elav.PU>Hsap\APP695.Scer\UAS.T:Hsap\MYC larvae. Co-expression of sraJF02557 or presence of sra1 does not enhance bouton number (synapse proliferation) or satellite bouton number at the NMJ in Scer\GAL4elav.PU>Hsap\APP695.Scer\UAS.T:Hsap\MYC larvae.

Co-expression of CanBJF02616 reduces Syt1 aggregate accumulations at NMJ axons and restores locomotor behavior in Scer\GAL4elav.PU>Hsap\APP695.Scer\UAS.T:Hsap\MYC larvae; co-expression of Pp2B-14DAct.Δ.Scer\UAS exacerbates these phenotypes. Co-expression of Pp2B-14DAct.Δ.Scer\UAS suppresses the ability of sraScer\UAS.T:Ivir\HA1 to protect against Scer\GAL4elav.PU>Hsap\APP695.Scer\UAS.T:Hsap\MYC induced larval axonal transport and locomotion defects.

sgg1 suppresses Syt1 aggregation in motor axons in the NMJ of Scer\GAL4elav.PU>Hsap\APP695.Scer\UAS.T:Hsap\MYC third instar larvae. sgg1 suppresses the effect of Pp2B-14DAct.Δ.Scer\UAS exacerbating the aggregation in motor axons in the NMJ of Scer\GAL4elav.PU>Hsap\APP695.Scer\UAS.T:Hsap\MYC third instar larvae. Co-expression of sggS9A.Scer\UAS does not affect Syt1 aggregation in motor axons in the NMJ of Scer\GAL4elav.PU>Hsap\APP695.Scer\UAS.T:Hsap\MYC third instar larvae.

The defects in the axonal pattern of s-LNv neurons in brains characteristic for adult flies expressing Tip60E431Q.Scer\UAS under the control of Scer\GAL4P2.4.Pdf are exacerbated further by co-expression of Hsap\APP695.Scer\UAS.T:Hsap\MYC and flies co-expressing Tip60E431Q.Scer\UAS with Hsap\APP695.Scer\UAS.T:Hsap\MYC show reduction in nighttime sleep with concomitant increase in daytime sleep (also seen in flies expressing either Tip60E431Q.Scer\UAS or Hsap\APP695.Scer\UAS.T:Hsap\MYC alone).

Simultaneous expression of Tip60Scer\UAS.cLa with Hsap\APP695.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4P2.4.Pdf has no effect on the axonal pattern of the s-LNv neurons in third instar larval brain, while it leads to a large increase in the area of the s-LNv neuron axonal arbor in the adult brain and it also rescues the nighttime sleep defects observed in adult flies expressing either of the transgenes alone.

Co-expression of Tip60E431Q.Scer\UAS and Hsap\APP695.Scer\UAS.T:Hsap\MYC both under the control of Scer\GAL4337Y results in 0% viability, with lethality occurring during the early second instar larval stage. Additionally, hatching of 100% of these larvae is delayed by 24-48 hours.

Complementation and Rescue Data
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Synonyms and Secondary IDs (2)
Reported As
Symbol Synonym
Hsap\APP695.Scer\UAS.T:Hsap\MYC
Hsap\APP695.UAS.Tag:MYC
Name Synonyms
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    References (15)