UASt regulatory sequences drive expression of a 1.9kb KpnI-XhoI fragment of Hsap\BACE1, which contains the entire open reading frame.
One copy of Df(2R)Egfr5 exacerbates the neurodegeneration seen in Alzheimer's disease modeled by expression of Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa.
No body wall contraction defects are seen in third instar larvae expressing Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4elav-C155. Larvae exhibit a significant reduction in crawling distance and rate compared to controls.
Expression of Hsap\BACE1Scer\UAS.cGa driven pan-neuronally by Scer\GAL4elav-C155 results in crumpled wings (in 61% of flies) and presence of melanotic masses on the abdomen and proboscis (26%); penetrance is around tenfold higher than is seen with expression of Hsap\APP695.Scer\UAS. Compared to genetic controls, Scer\GAL4elav-C155>Hsap\BACE1Scer\UAS.cGa young adults do not show significantly changes in survival.
Fly brains with expression of Hsap\BACE1Scer\UAS.cGa driven by Scer\GAL4elav-C155 show significant neuroanatomical changes: mushroom body calyx and lobe areas are significantly smaller than controls (or flies with expression of Hsap\APP695.Scer\UAS or Hsap\BACE1Scer\UAS.cLa) and Kenyon cell area is significantly smaller than is seen with expression of Hsap\BACE1Scer\UAS.cLa; in many cases, axons extending to the alpha lobes are shorter or missing. Flies (2-10 and 12-20 days old) with expression of Hsap\BACE1Scer\UAS.cGa driven by Scer\GAL4elav-C155 show a significant decrease in climbing ability compared to controls. Flies with expression of Hsap\BACE1Scer\UAS.cGa driven by Scer\GAL4elav-C155 show normal initial learning in a courtship conditioning paradigm, but unlike controls do not display short term memory (tested 2 minutes post training).
Expression of Hsap\BACE1Scer\UAS.cGa in photoreceptor neurons under the control of Scer\GAL4elav-C155 results in the degeneration of the highly organised architecture of retinal photoreceptors in an age-dependent manner.
Individuals simultaneously heterozygous for Df(2R)Egfr5 and expressing Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4Act.PU are short lived compared to controls.
Expression of Hsap\BACE1Scer\UAS.cGa in eyes under the control of Scer\GAL4GMR.PF does not cause retinal degeneration.
Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has abnormal locomotor behavior | third instar larval stage phenotype, enhanceable by Hsap\APP695.UAS, Scer\GAL4elav-C155
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act.PU has visible | adult stage phenotype, enhanceable by Df(2R)Egfr5/+
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act.PU has abnormal neuroanatomy | adult stage phenotype, enhanceable by Df(2R)Egfr5/+
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has short lived phenotype, suppressible | partially by IdeUAS.cTa, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has short lived phenotype, suppressible | partially by Hsap\IDEUAS.cTa, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI has visible phenotype, suppressible by IdeUAS.cTa, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI has visible phenotype, suppressible by Hsap\IDEUAS.cTa, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI
Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has abnormal neuroanatomy phenotype, suppressible by IdeUAS.cTa, Scer\GAL4elav-C155
Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has abnormal neuroanatomy phenotype, suppressible by Hsap\IDEUAS.cTa, Scer\GAL4elav-C155
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI has partially lethal - majority die phenotype, suppressible | partially by PsnC4/Psn[+]
Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 is a non-enhancer of abnormal neuroanatomy | adult stage | progressive phenotype of Hsap\APP695.UAS.Exel, Scer\GAL4elav-C155
Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 is a non-enhancer of abnormal neuroanatomy | adult stage | progressive phenotype of Hsap\APP695-Swedish.UAS.Tag:MYC, Scer\GAL4elav-C155
Hsap\BACE1UAS.cGa is a suppressor of abnormal neuroanatomy | third instar larval stage phenotype of Hsap\APPs.β.UAS.Tag:HA, SNF4Aγloe, Scer\GAL4Appl.G1a
IdeUAS.cTa, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 is a suppressor | partially of short lived phenotype of Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155
Hsap\IDEUAS.cTa, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 is a suppressor | partially of short lived phenotype of Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155
IdeUAS.cTa, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI is a suppressor of visible phenotype of Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI
Hsap\IDEUAS.cTa, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI is a suppressor of visible phenotype of Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI
Hsap\BACE1UAS.cGa, Scer\GAL4GMR.PF is a suppressor | partially of increased cell death phenotype of Hsap\APP695.UAS, Scer\GAL4GMR.PF
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has decreased rate of movement | adult stage phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav.Switch.PO has increased rate of movement | adult stage | RU486 conditional phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has visible | adult stage phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has abnormal neuroanatomy | adult stage phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has melanotic mass phenotype | adult stage phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has abnormal memory | adult stage phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has abnormal size | adult stage phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has abnormal locomotor behavior | adult stage | progressive phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has short lived phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI has visible phenotype
Hsap\APP695.UAS.Exel, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has abnormal learning | adult stage | progressive phenotype
Hsap\APP695.UAS.Exel, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has abnormal memory | adult stage | progressive phenotype
Df(2R)Egfr5/+, Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act.PU has short lived phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act.PU has wing vein phenotype, enhanceable by Df(2R)Egfr5/+
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act.PU has brain | adult stage phenotype, enhanceable by Df(2R)Egfr5/+
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI has wing vein | ectopic phenotype, enhanceable by Psn+14.UAS, Scer\GAL4Act5C.PI
Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has eye photoreceptor cell phenotype, suppressible by IdeUAS.cTa, Scer\GAL4elav-C155
Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has eye photoreceptor cell phenotype, suppressible by Hsap\IDEUAS.cTa, Scer\GAL4elav-C155
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI has wing vein | ectopic phenotype, suppressible by IdeUAS.cTa, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI has wing vein | ectopic phenotype, suppressible by Hsap\IDEUAS.cTa, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI has wing vein | ectopic phenotype, suppressible | partially by PsnC4/Psn[+]
Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 is a non-enhancer of adult brain | progressive phenotype of Hsap\APP695.UAS.Exel, Scer\GAL4elav-C155
Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 is a non-enhancer of adult brain | progressive phenotype of Hsap\APP695-Swedish.UAS.Tag:MYC, Scer\GAL4elav-C155
Hsap\BACE1UAS.cGa is a suppressor of larval brain | third instar larval stage phenotype of Hsap\APPs.β.UAS.Tag:HA, SNF4Aγloe, Scer\GAL4Appl.G1a
IdeUAS.cTa, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI is a suppressor of wing vein | ectopic phenotype of Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI
Hsap\IDEUAS.cTa, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI is a suppressor of wing vein | ectopic phenotype of Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI
Hsap\BACE1UAS.cGa, Scer\GAL4GMR.PF is a suppressor | partially of eye photoreceptor cell phenotype of Hsap\APP695.UAS, Scer\GAL4GMR.PF
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has type I bouton phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has wing | adult stage phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has mushroom body | adult stage phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4elav-C155 has proboscis | adult stage phenotype
Hsap\APP695.UAS, Hsap\BACE1UAS.cGa, Scer\GAL4Act5C.PI has wing vein | ectopic phenotype
Co-expression of Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa driven by Scer\GAL4elav.Switch.PO driven by Scer\GAL4elav.Switch.PO (with 200um RU486) results in significant hyperactivity (including nocturnal hyperactivity followed by a rapid decline, the effect is more prominent in male flies, and the effect disappears as flies age); this effect is more striking on a diet with a high carbohydrate to protein ratio (compared to low carbohydrate to protein ratio).
Co-expression of Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa driven by Scer\GAL4elav-C155 results in significant hypoactivity compared to controls, though total activity at night is not significantly altered (it is significantly decreased during the day).
Larvae co-expressing Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa 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.cGa is expressed under the control of Scer\GAL4elav-C155 are enhanced upon co-expression of Hsap\APP695.Scer\UAS.
Co-expression of Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4elav-C155 results in structural changes in the synapse of the third instar larval muscle 6 and 7 neuromuscular junctions (NMJs). The overall number of boutons is reduced compared to controls, and this is due to a reduced number of type 1s boutons; the number of 1b boutons is similar to wild type. Both the number of motor neuron branches and the size of muscles 6 and 7 at the NMJ are similar to controls. The density of presynaptic release sites (brp-positive active zones) in motor neurons is also normal, but mitochondrial localisation defects are observed.
Expression of both Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4elav-C155 leads to a subset of flies showing melanotic masses on the ventral proboscis, curled wings, and these flies show a significant and progressive defect in climbing ability beginning at 42 days post-eclosion, a significant decrease in the size of the mushroom body, and a significant decrease in immediate recall memory in a conditioned courtship suppression assay, but do not show a significant decrease in lifespan nor any significant defect in learning ability as compared to controls.
Co-expression of Hsap\BACE1Scer\UAS.cGa suppresses the increase in vacuolisation seen when Hsap\APP695.Scer\UAS.Exel is expressed in the brains of SNF4Aγloe mutant third instar larvae under the control of Scer\GAL4Appl.G1a.
The pan-neuronal co-expression of Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4elav-C155 leads to a decrease in adult lifespan, as compared to controls.
Forced expression of IdeScer\UAS.cTa under the control of Scer\GAL4elav-C155 can suppress the neuronal degeneration induced by the expression of Hsap\BACE1Scer\UAS.cGa.
Forced expression of Hsap\IDEScer\UAS.cTa under the control of Scer\GAL4elav-C155 can suppress the neuronal degeneration induced by the expression of Hsap\BACE1Scer\UAS.cGa.
Co-expression of Hsap\BACE1Scer\UAS.cGa and Hsap\APP695.Scer\UAS under the control of Scer\GAL4elav-C155 results in reduced lifespan compared with controls.
The reduced lifespan of flies co-expressing Hsap\BACE1Scer\UAS.cGa and Hsap\APP695.Scer\UAS under the control of Scer\GAL4elav-C155 is partially suppressed by the co-expression of IdeScer\UAS.cTa.
The reduced lifespan of flies co-expressing Hsap\BACE1Scer\UAS.cGa and Hsap\APP695.Scer\UAS under the control of Scer\GAL4elav-C155 is partially suppressed by the co-expression of Hsap\IDEScer\UAS.cTa.
The ectopic wing vein phenotype induced by co-expressing Hsap\BACE1Scer\UAS.cGa and Hsap\APP695.Scer\UAS under the control of Scer\GAL4Act5C.PI is suppressed by the co-expression of IdeScer\UAS.cTa.
The ectopic wing vein phenotype induced by co-expressing Hsap\BACE1Scer\UAS.cGa and Hsap\APP695.Scer\UAS under the control of Scer\GAL4Act5C.PI is suppressed by the co-expression of Hsap\IDEScer\UAS.cTa.
The loss of tissue due to age-progressive neurodegeneration (vacuolar lesions) observed in the brains of adult flies expressing either Hsap\APP695.Scer\UAS.Exel or Hsap\APP695-Swedish.Scer\UAST:Hsap\MYC under the control of Scer\GAL4elav-C155 is not significantly affected by co-expression of Hsap\BACE1Scer\UAS.cGa. Flies expressing either Hsap\APP695.Scer\UAS.Exel or Hsap\APP695-Swedish.Scer\UAST:Hsap\MYC alone or in combination with Hsap\BACE1Scer\UAS.cGa display strong age-progressive defects.
One copy of Df(2R)Egfr5 enhances the wing vein phenotype seen when Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa are co-expressed under the control of Scer\GAL4Act.PU. The neurodegeneration is also increased, with at least 50% of flies showing clear evidence of neurodegeneration throughout the central brain compared to ~10% in controls and, unlike in controls, a significant fraction show dramatic loss of brain tissue.
The survival rates and wing patterns are not affected when flies coexpress Psn+14.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4Act5C.PI.
Coexpression of Hsap\BACE1Scer\UAS.cGa and Hsap\APP695.Scer\UAS, under the control of Scer\GAL4GMR.PF, leads to a retinal degeneration phenotype that is less severe than that seen when Hsap\APP695.Scer\UAS is expressed alone.
Flies that coexpress Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4Act5C.PI exhibit ectopic wing veins. This phenotype is enhanced in flies that express Psn+14.Scer\UAS in addition to Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4Act5C.PI.
A PsnC4/+ background partially rescues the ectopic wing vein formation and semi-lethality of flies that coexpress Hsap\APP695.Scer\UAS and Hsap\BACE1Scer\UAS.cGa under the control of Scer\GAL4Act5C.PI.