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.
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has abnormal neuroanatomy phenotype, enhanceable by CatKK101528, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has visible | adult stage phenotype, enhanceable by CanA1JF01871, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has visible | adult stage phenotype, enhanceable by CanBJF02616, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has visible | adult stage phenotype, enhanceable by sraEY07182, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has abnormal neuroanatomy | larval stage phenotype, enhanceable by sraEY07182, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has increased cell death | larval stage phenotype, enhanceable by sraEY07182, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has visible | adult stage phenotype, enhanceable by sraUAS.cEa, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has increased cell death | adult stage phenotype, suppressible by Tip60UAS.cLa, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has abnormal learning | third instar larval stage phenotype, suppressible by Tip60UAS.cLa, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has abnormal short-term memory | third instar larval stage phenotype, suppressible by Tip60UAS.cLa, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has abnormal short-term memory | adult stage phenotype, suppressible by Tip60UAS.cLa, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has abnormal locomotor behavior | larval stage phenotype, suppressible by Tip60UAS.cLa, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has abnormal locomotor behavior | adult stage phenotype, suppressible by Tip60UAS.cLa, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has short lived phenotype, suppressible by Tip60UAS.cLa, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has increased cell death | adult stage phenotype, suppressible by egrGD12658, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has increased cell death | adult stage phenotype, suppressible by egrKK103432, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has abnormal locomotor behavior | adult stage phenotype, suppressible by egrKK103432, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has abnormal locomotor behavior | adult stage phenotype, suppressible by egrGD12658, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has short lived phenotype, suppressible by egrKK103432, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has short lived phenotype, suppressible by egrGD12658, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has short lived phenotype, suppressible by domk08108/l(3)hem2
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has abnormal neuroanatomy phenotype, suppressible by domk08108/l(3)hem2
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav.PU has abnormal locomotor behavior | adult stage | progressive phenotype, suppressible by Hsap\CCN2UAS.cYa, Scer\GAL4elav.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav.PU has abnormal memory | adult stage | progressive phenotype, suppressible by Hsap\CCN2UAS.cYa, Scer\GAL4elav.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has visible | adult stage phenotype, suppressible by sraKO
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has adult brain phenotype, enhanceable by CatKK101528, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has embryonic/larval plasmatocyte | adult stage phenotype, enhanceable by CatKK101528, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has eye phenotype, enhanceable by sraEY07182, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has eye disc | larval stage phenotype, enhanceable by sraEY07182, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has eye phenotype, enhanceable by CanA1JF01871, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has eye phenotype, enhanceable by CanBJF02616, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has photoreceptor neuron | larval stage phenotype, enhanceable by sraEY07182, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has axon | third instar larval stage phenotype, enhanceable by sraEY07182, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has larval brain phenotype, enhanceable by sraEY07182, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has eye phenotype, enhanceable by sraUAS.cEa, Scer\GAL4GMR.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has adult Kenyon cell phenotype, suppressible by Tip60UAS.cLa, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has mushroom body phenotype, suppressible by Tip60UAS.cLa, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has adult brain phenotype, suppressible by egrKK103432, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has adult brain phenotype, suppressible by egrGD12658, Scer\GAL4elav-C155
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has adult brain phenotype, suppressible by domk08108/l(3)hem2
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav-C155 has embryonic/larval plasmatocyte | adult stage phenotype, suppressible by domk08108/l(3)hem2
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has ommatidium | adult stage | progressive phenotype, suppressible by Scer\GAL4elav.PU/Hsap\CCN2UAS.cYa
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has rhabdomere | adult stage | progressive phenotype, suppressible by Scer\GAL4elav.PU/Hsap\CCN2UAS.cYa
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has ommatidium | adult stage | progressive phenotype, suppressible by Hsap\CCN2repo.PY
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has rhabdomere | adult stage | progressive phenotype, suppressible by Hsap\CCN2repo.PY
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav.PU has adult brain phenotype, suppressible | partially by Hsap\CCN2UAS.cYa, Scer\GAL4elav.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4elav.PU has neuron | adult stage phenotype, suppressible | partially by Hsap\CCN2UAS.cYa, Scer\GAL4elav.PU
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has eye phenotype, suppressible by sraKO
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has ommatidium | adult stage | progressive phenotype, non-suppressible by Mmp1JF01336/Scer\GAL4elav.PU/Hsap\CCN2UAS.cYa
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has rhabdomere | adult stage | progressive phenotype, non-suppressible by Mmp1JF01336/Scer\GAL4elav.PU/Hsap\CCN2UAS.cYa
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has ommatidium | adult stage | progressive phenotype, non-suppressible by Scer\GAL4elav.PU/Hsap\CCN2UAS.cYa/Mmp2JF01337
Hsap\APPAβ42.UAS.cBa, Scer\GAL4GMR.PU has rhabdomere | adult stage | progressive phenotype, non-suppressible by Scer\GAL4elav.PU/Hsap\CCN2UAS.cYa/Mmp2JF01337
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.
Made by Juan Botas (Baylor College of Medicine).