UASt regulatory sequences drive expression of the Hsap\APP Aβ40 peptide, tagged at the N-terminal end with the Tag:SS(rPENK) signal sequence.
Neuronal expression of Aβ40 peptide in transgenic flies induces progressive learning defects, but does not result in the formation of diffused Aβ deposits and the flies do not show locomotor dysfunction, progressive neurodegeneration or premature death.
Expression of Hsap\APPAβ40.Scer\UAS.T:Rnor\PENK, either pre- or post-synaptically, under the control of Scer\GAL4elav-C155 or Scer\GAL4G7 respectively, does not cause any change in EJC amplitude.
Expression of Hsap\APPAβ40.Scer\UAS under the control of Scer\GAL4ChAT.7.4 does not result in a significant decrease in lifespan or climbing ability, nor any obvious defects in neuronal morphology, as compared to controls.
2- to 3-day old adults expressing Hsap\APPAβ40.Scer\UAS.T:Rnor\PENK under the control of Scer\GAL4elav-C155 do not show any significant defects in a Pavlovian olfactory learning assay. The flies being to show a subtle, but statistically significant, learning defect at 6-7 days old, and the decline is most obvious in 14-15 day old flies. Learning defects are seen only in males but not in females (consistent with higher expression of Hsap\APPAβ40.Scer\UAS.T:Rnor\PENK in the male flies). Odour avoidance (to methylcyclohexanol) and electric shock reactivity is normal in 14- to 15-day old flies expressing Hsap\APPAβ40.Scer\UAS.T:Rnor\PENK under the control of Scer\GAL4elav-C155. Adults expressing Hsap\APPAβ40.Scer\UAS.T:Rnor\PENK under the control of Scer\GAL4elav-C155 show the same climbing ability as control flies, even 3 weeks after eclosion. The lifespan of flies expressing Hsap\APPAβ40.Scer\UAS.T:Rnor\PENK under the control of Scer\GAL4elav-C155 is the same as that of control flies. Aged adult flies expressing Hsap\APPAβ40.Scer\UAS.T:Rnor\PENK under the control of Scer\GAL4elav-C155 do not show neurodegeneration in the brain.