UASt regulatory sequences drive expression of mature length Oari\PrP (amino acid residues 25-231) encoding the naturally occurring "VRQ" polymorphic variant (Val[136] Leu[141] Arg[154] Gln[171]). The protein is flanked at the N-terminal end by an insect secretion signal peptide and at the C-terminal end by the Oari\PrP glycosylphosphatidylinositol anchor signal sequence.
Zzzz\PrPVRQ.Scer\UAS flies are exposed to (fed) ovine scrapie prion inocula during the larval stage in order to model prion disease. These flies show shortened survival time compared to controls, though no significant reduction in locomotor activity is observed.
Unlike controls, flies expressing Oari\PrPVRQ.UAS under the control of either Scer\GAL4elav-C155 or Scer\GAL4Act5C.PI and infected at the larval stage with PG127 or Apl[[338]] prions support prion propagation and support additional fly-to-mouse prion propagation; these flies also show a progressive decrease in climbing ability, which is much more severe than in infected controls. There is also fly-to-fly-to-mouse propagation of PG127 prions in the Scer\GAL4elav-C155m driver background.
The expression of Oari\PrPVRQ.Scer\UAS under the control of Scer\GAL4elav-C155 results in a decrease in adult lifespan compared to controls.
Adults expressing Zzzz\PrPVRQ.Scer\UAS under the control of Scer\GAL4elav-C155 and exposed to VRQ/VRQ scrapie-infected sheep brain homogenate at the larval stage by oral exposure show a do not show an accelerated decline in locomotor activity with age compared to animals expressing Zzzz\PrPVRQ.Scer\UAS under the control of Scer\GAL4elav-C155 and exposed to control (scrapie-negative) VRQ/VRQ sheep brain material.
Adults expressing Zzzz\PrPVRQ.Scer\UAS under the control of Scer\GAL4elav-C155 and exposed to VRQ/VRQ scrapie-infected sheep brain homogenate at the larval stage by oral exposure show a significantly enhanced mortality rate compared to animals expressing Zzzz\PrPVRQ.Scer\UAS under the control of Scer\GAL4elav-C155 and exposed to control (scrapie-negative) VRQ/VRQ sheep brain material.