UASt regulatory sequences drive expression of the Tag:SS(nec) secretory signal peptide followed by two tandem copies of the Aβ (amyloid β) monomer linked together by a 12 amino acid linker peptide. Both copies of Aβ are the 42 amino acid residue form.
10-32 day old flies expressing Hsap\APPT12.Aβ42.Scer\UAS under the control of Scer\GAL4tim.PE exhibit significant arrhythmic behavior in constant dark conditions (DD) compared to controls. This arrhythmia is partially rescued when expression is suppressed in glial cells using Scer\GAL80repo.PL although flies still show reduced rhythmicity compared to controls. Loss of Pdf expressing sLNv and ILNv clock neurons is seen. Overall locomotor activity is unaffected. No phenotypes are seen up to 30 days post eclosion when Hsap\APPT12.Aβ42.Scer\UAS is expressed under the control of Scer\GAL4P2.4.Pdf. Restricting expression of Hsap\APPT12.Aβ42.Scer\UAS to non-Pdf expressing clock cells under the control of Scer\GAL4tim.PE and Scer\GAL80Pdf.PS has no effect on the number of Pdf expressing sLNV and ILNv neurons.
Flies expressing Hsap\APPT12.Aβ42.Scer\UAS under the control of Scer\GAL4GMR.PF form significant quantities of large, SDS-insoluble deposits in the head.
Flies expressing Hsap\APPT12.Aβ42.Scer\UAS under the control of Scer\GAL4GMR.PF have severe eye malformation with loss of the ommatidial arrays and the appearance of melanised patches of necrotic tissue.
Flies expressing one copy of Hsap\APPT12.Aβ42.Scer\UAS under the control of Scer\GAL4elav-C155 have a significantly shorter lifespan than wild-type controls and than flies expressing two copies of Hsap\APPAβ42.Scer\UAS.att under the control of Scer\GAL4elav-C155.
