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General Information
Symbol
Hsap\APPAβ42.UAS.cUa
Species
H. sapiens
Name
FlyBase ID
FBal0295570
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
UAS-Aβ42, Aβ42, Aβ42
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
UAS regulatory sequences drive expression of a Hsap\APP Aβ42 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 )
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference
Expression of Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU results in a severe reduction in the size of the adult eye as compared to wild type, and the eye has a glazed appearance due to the fusion of lenses; third instar eye discs from these mutants show a significant increase in cell death and defective axonal targeting of the retinal neurons, as compared to controls.
Expression of Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4elav-C155 results in age-progressive neurodegeneration (vacuole lesions in the brain of aged adult flies) and earlier and more severe age-related decline in climbing ability.
Flies expressing Hsap\APPAβ42.Scer\UAS.cUa in the central nervous system under the control of Scer\GAL4elav.PU display disease phenotypes, including reduced longevity and a gradual decline of locomotive ability. Feeding flies with compound D737 (C[[25]]H[[20]]N[[2O]]) increases longevity of the flies compared with controls. Similarly, feeding flies with D737 analogues D744, D830, D979 and D742 also results in improved longevity. The most effective of these compounds (D744) produces a life span curve for the transgenic flies that is fairly close to that of wild-type. Compound D737 and all four analogues also ameliorate the climbing defects in the transgenic flies.
Expression of Hsap\APPAβ42.Scer\UAS.cUa in the wing, under the control of Scer\GAL4Bx-MS1096, generates ectopic and defective wing vein formation. Addition of KSOP1009 to the food media suppresses defective wing vein formation. Addition of PD98059 to the food media suppresses defective wing vein formation. Expression of Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4elav-C155 decreases climbing ability, compared to wild-type flies. Addition of 50υM PD98059 to the food media for these flies restores climbing ability. Addition of 5υg/mL KSOP1009 also restores climbing ability in these flies. Pan-neuronal expression of Hsap\APPAβ42.Scer\UAS.cUa, under the control of Scer\GAL4elav-C155, increases the number of glial cells in the larval brain. Addition of 5υg/mL KSOP1009 to fly media almost completely restores the number of glial cells in mutant larval brains to control levels. Addition of PD98059 does not affect glial cell proliferation.
Expression of Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU results in reduced eyes with a glazed surface. Mutant eye imaginal discs show an almost three-fold increase in TUNEL-positive cells compared to controls. Aberrant axonal targeting from the retina to the brain is seen, with the retinal axons failing to innervate the medulla and lamina and ending abruptly.
Scer\GAL4elav.PU-mediated expression of Hsap\APPAβ42.Scer\UAS.cUa increases apoptosis in the larval brain. Scer\GAL4elav.PU, Hsap\APPAβ42.Scer\UAS.cUa flies have impaired climbing ability.
Female flies expressing Hsap\APPAβ42.Scer\UAS.cUa in the developing nervous system, under the control of Scer\GAL4elav-C155, show reduced longevity and exhibit a gradual decline in locomotive ability.
Defects can be seen in the third larval instar eye disc in animals expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU. Improper spacing of the differentiating photoreceptors and mild fusion of the ommatidial clusters is seen. At the prepupal stage, mild to stronger fusion of the ommatidial clusters is seen resulting in clumps of photoreceptors and loss of photoreceptors in the ommatidium. The phenotype becomes progressively more severe during the pupal stage, with multiple fusions of ommatidia and holes in the retina where ommatidial clusters have been extruded. The adult eye is severely diminished in size and shows ommatidial fusion, which in severe cases leads to a glazed appearance. The retina of the adult eye is very thin, has poorly differentiated photoreceptors and is vacuolated, and the overlying lenses are fused with it. TUNEL positive cells begin to appear as early as the late third larval instar in the eye discs of animals expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU.
Motor neurons of larvae expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4Toll-6-D42 display normal axonal transport. Expression of Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4Toll-6-D42 leads to subtle morphological aberrations of larval neuromuscular junctions (NMJs) which includes the appearance of "satellite" boutons and thinning of inter-bouton regions. The locomotor performance of flies expressing Scer\GAL4unspecified>Hsap\APPAβ42.Scer\UAS.cUa is similar to that of control flies until they are about 12 days old, after which their climbing abilities undergo a steady age-related deterioration.
External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement
Reference
Suppressed by
Statement
Reference
NOT suppressed by
Enhancer of
Other
Phenotype Manifest In
Enhanced by
Statement
Reference
Suppressed by
Statement
Reference
NOT suppressed by
Enhancer of
Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference
Co-expression of nejScer\UAS.T:SV5\V5, nejΔQ.Scer\UAS, nejΔHQ.Scer\UAS, nejΔNZK.Scer\UAS or nejKIX.Scer\UAS, but not nejdsRNA.Scer\UAS.cKa, partially rescues the small eye and lens fusion phenotype seen in adult flies expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU. Co-expression of nejScer\UAS.T:SV5\V5, nejΔQ.Scer\UAS, nejΔHQ.Scer\UAS, nejΔNZK.Scer\UAS, nejKIX.Scer\UAS or nejdsRNA.Scer\UAS.cKa partially suppresses the increased cell death; and co-expression of nejScer\UAS.T:SV5\V5 suppresses the aberrant axonal targeting observed in third instar eye discs of flies expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU. Co-expression of nejΔBHQ.Scer\UAS enhances the eye phenotype of adult flies, enhances the increased cell death and aberrant axonal targeting observed in third instar eye disc of flies expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU, and results in failure of these flies to eclose.
A Amph5E3 mutant background does not affect the subtle rough eye phenotype caused by expression of Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4elav-C155.
Co-expression of crbGD14463 significantly rescues the eye neurodegeneration phenotype caused by expression of Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU. The increased cell death phenotype which is seen in the eye imaginal discs of animals expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU is also significantly suppressed. crb11A22 significantly rescues the eye neurodegeneration phenotype caused by expression of Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU. The increased cell death phenotype which is seen in the eye imaginal discs of animals expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU is also significantly suppressed. Co-expression of crbScer\UAS.cWa enhances the increased cell death phenotype which is seen in the eye imaginal discs of animals expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU. The increased cell death phenotype which is seen in the eye imaginal discs of animals expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU is also significantly enhanced. Co-expression of either crbIntraΔERLI.Scer\UAS.T:Hsap\MYC, crbIntraY10A.E16A.Scer\UAS.T:Hsap\MYC or crbIntraY10A.E16A.ΔERLI.Scer\UAS.T:Hsap\MYC rescues the adult eye neurodegeneration phenotype seen in animals expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU. The increased cell death phenotype which is seen in the eye imaginal discs of animals expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU is also significantly suppressed.
Co-expression of BacA\p35Scer\UAS.cHa partially rescues the increase in cell death seen in the third larval instar eye disc of animals expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU. There is a subtle rescue of the reduced eye size phenotype in the adult, but the neurodegenerative eye phenotype is still present in adult flies. Co-expression of pucScer\UAS.cMa significantly rescues the increase in cell death seen in the third larval instar eye disc of animals expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU and also strongly rescues the neurodegenerative phenotype of the adult eye. Co-expression of hepAct.Scer\UAS.cUa enhances the increase in cell death seen in the third larval instar eye disc of animals expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU and results in adults having a "no-eye" phenotype. Co-expression of JraAsp.B.Scer\UAS enhances the increase in cell death seen in the third larval instar eye disc of animals expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU and results in adults having a severe reduced eye phenotype. Co-expression of bskDN.Scer\UAS dramatically rescues the increase in cell death seen in the third larval instar eye disc of animals expressing Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4GMR.PU and also strongly rescues the reduced size of the adult eye.
Co-expression of Hsap\APPAβ42.Scer\UAS.cUa with Hsap\MAPTScer\UAS.1N4R under the control of Scer\GAL4Toll-6-D42 enhances the axonal transport phenotype resulting from the expression of Hsap\MAPTScer\UAS.1N4R alone. Co-expression of Hsap\APPAβ42.Scer\UAS.cUa with Hsap\MAPTScer\UAS.1N4R under the control of Scer\GAL4Toll-6-D42 exacerbates the neuromuscular junction (NMJ) aberrations seen in mutants expressing any one of the transgenes alone, with more evidence of both "satellite" boutons and thinning of the inter-bouton regions. Co-expression of Hsap\APPAβ42.Scer\UAS.cUa with Hsap\MAPTR406W.Scer\UAS.1N4R under the control of Scer\GAL4Toll-6-D42 exacerbates the neuromuscular junction (NMJ) aberrations seen in mutants expressing Hsap\APPAβ42.Scer\UAS.cUa alone resulting in a very extreme form of the phenotype. Co-expression of Hsap\MAPTScer\UAS.1N4R and Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4unspecified enhances the locomotor impairment of flies expressing Scer\GAL4unspecified>Hsap\MAPTScer\UAS.1N4R alone. As the double transgenic flies age, their climbing abilities steadily deteriorate. Co-expression of Hsap\MAPTScer\UAS.1N4R and Hsap\APPAβ42.Scer\UAS.cUa under the control of Scer\GAL4unspecified enhances the longevity phenotypes that are seen in flies expressing any of the two transgenes alone. LiCl treatment ameliorates the survival defects.
Complementation and Rescue Data
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Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (3)
Reported As
Symbol Synonym
Hsap\APPAβ42.Scer\UAS.cUa
Hsap\APPAβ42.UAS.cUa
Name Synonyms
Secondary FlyBase IDs
    References (13)