FB2024_03 , released June 25, 2024
Allele: Hsap\APPAβ42.UAS.cBa
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General Information
Symbol
Hsap\APPAβ42.UAS.cBa
Species
H. sapiens
Name
FlyBase ID
FBal0256662
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
UAS-Aβ42
Key Links
Transgenic product class
Nature of the Allele
Transgenic product class
Progenitor genotype
Carried in construct
Cytology
Description

UASt regulatory sequences drive expression of the 42 amino acid Aβ fragment from Hsap\APP tagged at the N-terminal end with a secretion signal peptide from aos.

UAS drives expression of the 42 amino acid Aβ fragment from Hsap\APP.

Allele components
Component
Use(s)
Encoded product / tool
Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
Variant Molecular Consequences
Associated Sequence Data
DNA sequence
Protein sequence
 
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 exacerbated by CG7896KK105990
is ameliorated by CG5567GD11694
is ameliorated by CG8888EY12413
is ameliorated by CG6154MI08916
is ameliorated by CG7137GD12147
is ameliorated by ContGD12610
is exacerbated by Cox11KK100158
is ameliorated by sroGD7469
is ameliorated by Dgkεox-1
is exacerbated by E2f1KK100304
is ameliorated by Hydr2MI08405
is ameliorated by ThgGD11217
is ameliorated by kek3GD1733
is ameliorated by kek5MI01444
is exacerbated by plxKK100306
is ameliorated by Tip60UAS.cLa
is ameliorated by AcerΔ168
is exacerbated by PtenUAS.cUa
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Expression of Hsap\APPAβ42.UAS.cBa under the control of Scer\GAL4elav-C155 leads to diffuse amyloid deposits that do not appear in abundance in the mushroom body (MB) until flies are aged to at least 25 days.

Expression of Hsap\APPAβ42.UAS.cBa under the control of Scer\GAL4elav-C155 leads to higher level of apoptotic neuronal cell death in the MB Kenyon cell region in the adult (28-days-old) brain.

Expression of Hsap\APPAβ42.UAS.cBa under the control of Scer\GAL4elav-C155 leads to defects in both learning (in third instar larvae) and short term memory (in third instar larvae and adults).

Expression of Hsap\APPAβ42.UAS.cBa under the control of Scer\GAL4elav-C155 leads to defects in larval locomotion (line crossing, righting, and contraction assays) and adult locomotion (negative geotaxis assay).

Expression of Hsap\APPAβ42.UAS.cBa under the control of Scer\GAL4elav.PLu leads to impaired jumping performance, late onset locomotory deficit (impaired negative geotaxis), increased oxidative stress (in terms of increased ROS level in mitochondria and reduction in mitochondrial membrane potential) and increase in mitochondrial mediated apoptosis when compared to control flies.

Adult flies expressing Hsap\APPAβ42.Scer\UAS.cBa under the control of Scer\GAL4elav-C155 display a significant increase in vacuolar degeneration and increased apoptosis in the brain, decreased lifespan, show significant recruitment of plasmatocytes to the postero-dorsal site of the brain near the mushroom body lobe (although they do not infiltrate the brain and there is no significant increase in the total population of plasmatocytes), and a reduction in locomotor activity, as compared to controls. These phenotypes become more pronounced in response to infection with the pathogenic enterobacteria Ecc15 or Pseudomonas entomophila, whereas control flies do not exhibit any of these phenotypes upon Ecc15 or Pseudomonas infection. Flies expressing Hsap\APPAβ42.Scer\UAS.cBa under the control of Scer\GAL4elav-C155 also show an increase in reactive oxygen species stress, this phenotype becomes more pronounced upon infection with Ecc15, whereas control flies do not exhibit any oxidative stress upon Ecc15 infection.

Expression of Hsap\APPAβ42.Scer\UAS.cBa under the control of Scer\GAL4elav.PU results in accumulation of Hsap\APP-positive puncta and neuronal loss in the adult brain and the flies also display memory loss (assayed under an olfactory associative learning paradigm) as well as age-progressive decrease in climbing ability, as compared to controls. Scer\GAL4GMR.PU-driven expression leads to a progressive photoreceptor degeneration in the adult eye manifested by disorganization of ommatidial lattice and rhabdomere loss.

Expression of Hsap\APPAβ42.Scer\UAS.cBa driven by Scer\GAL4ninaE.PT (crosses carried out at 18[o]C and shifted to 25[o]C following eclosion) does not significantly affect external eye morphology in adult flies. At 1 and 30 days old (but not 10), electroretinogram (ERG) recordings of light induced potentials from Scer\GAL4ninaE.PT>Hsap\APPAβ42.Scer\UAS.cBa flies show a significant increase in light-evoked in depolarization amplitude compared to controls; mutant flies show significant increases in ON transient amplitude at day 1, 10 and 30 and a significant increase in OFF transient amplitude at day 1.

The number and morphology of photoreceptors (retinae show intact ommatidia with 7 visible rhabdomeres) in Scer\GAL4ninaE.PT>Hsap\APPAβ42.Scer\UAS.cBa flies is grossly preserved at day 1, similar to controls; with aging (day 10 and 30), progressive vacuolar changes affect the retina and there is a significant decrease in rhabdomere numbers at day 30. Photoreceptor ultrastructure (examined with TEM) in 10 day old Scer\GAL4ninaE.PT>Hsap\APPAβ42.Scer\UAS.cBa flies revealed significant subtle defects and irregularities in rhabdomeres (splitting or fraying at edges, vacuolar changes). Mutants at day 10 have similar numbers of mitochondria per ommatidium and percentage of photoreceptors with electron dense vacuoles (telolysosomes) as controls, but have a significant increase in the number of autophagic vacuoles (increased numbers of multivesicular or multilamellar bodies). Scer\GAL4ninaE.PT>Hsap\APPAβ42.Scer\UAS.cBa flies do not show significant disruption of photoreceptor synaptic terminal organization and morphology at 10 days old compared to controls.

Expression of Hsap\APPAβ42.Scer\UAS under the control of Scer\GAL4GMR.PU results in a severe small and rough-eye phenotype in adult flies, increased levels of cell death and neurodegeneration of photoreceptor neurons in larval eye disc as well as photoreceptor targeting defects in the larval brain.

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

Co-expression of egrGD12658 partially suppresses the increased cell death in the brain, the climbing defects, and the shortened lifespan seen in Ecc15-infected flies expressing Hsap\APPAβ42.Scer\UAS.cBa under the control of Scer\GAL4elav-C155.

Co-expression of egrKK103432 partially suppresses the increased cell death in the brain, the climbing defects, and the shortened lifespan seen in Ecc15-infected flies expressing Hsap\APPAβ42.Scer\UAS.cBa under the control of Scer\GAL4elav-C155.

The presence of both l(3)hem2 and domk08108 completely suppresses the shortened lifespan and recruitment of plasmatocytes to the postero-dorsal site of the brain near the mushroom body lobe, and partially suppresses the neurodegeneration seen in Ecc15 infected flies that express Hsap\APPAβ42.Scer\UAS.cBa under the control of Scer\GAL4elav-C155.

Co-expression of CatKK101528 leads to a significant increase in recruitment of plasmatocytes to the brain in flies that express Hsap\APPAβ42.Scer\UAS.cBa under the control of Scer\GAL4elav-C155.

The Hsap\APP protein accumulations and neuronal loss in adult brain along with the age-progressive memory loss and climbing ability deficit characteristic for adult flies expressing Hsap\APPAβ42.Scer\UAS.cBa under the control of Scer\GAL4elav.PU can be at least partially rescued by co-expression of Hsap\CTGFUAS.cYa.

Similarly, the progressive photoreceptor degeneration in the adult eye observed upon Scer\GAL4GMR.PU-driven expression of Hsap\APPAβ42.Scer\UAS.cBa can be significantly suppressed either by co-expression of Hsap\CTGFUAS.cYa or by combination with Hsap\CTGFrepo.PY (expressed in glial cells) but not by co-expression of Hsap\CTGFUAS.cYa combined with either Mmp1JF01336 or Mmp2JF01337.

The severe rough eye phenotype in adults as well as the increased levels of cell death in the larval eye disc observed in flies expressing Hsap\APPAβ42.Scer\UAS.cBa under the control of Scer\GAL4GMR.PU are exacerbated further by co-expression of sraEY07182.

The severe small and rough eye phenotype observed in flies expressing Hsap\APPAβ42.Scer\UAS.cBa under the control of Scer\GAL4GMR.PU is exacerbated further by co-expression of sraScer\UAS.cEa.

The severe small and rough eye phenotype observed in flies expressing Hsap\APPAβ42.Scer\UAS.cBa under the control of Scer\GAL4GMR.PU is significantly ameliorated by combination with sraKO in heterozygous state.

The neurodegeneration of photoreceptor neurons in larval eye disc as well as the photoreceptor axon targeting defects in the brain observed in larvae expressing either Hsap\APPAβ42.Scer\UAS or sraEY07182 under the control of Scer\GAL4GMR.PU are significantly enhanced when the two transgenes are co-expressed.

The small and rough eye phenotype observed in flies expressing Hsap\APPAβ42.Scer\UAS.cBa under the control of Scer\GAL4GMR.PU is exacerbated further by co-expression of CanA1JF01871 RNAi.

The small and rough eye phenotype observed in flies expressing Hsap\APPAβ42.Scer\UAS.cBa under the control of Scer\GAL4GMR.PU is exacerbated further by co-expression of CanBJF02616 RNAi.

Complementation and Rescue Data
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Mutant
Wild-type
Stocks (4)
Notes on Origin
Discoverer
Comments
Comments

Made by Juan Botas (Baylor College of Medicine).

External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (2)
Reported As
Symbol Synonym
Hsap\APPAβ42.Scer\UAS.cBa
Hsap\APPAβ42.UAS.cBa
Name Synonyms
Secondary FlyBase IDs
    References (31)