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FB2026_02
,
released June 18, 2026
UASt regulatory sequences drive expression of mature length Oari\PrP (amino acid residues 25-231) encoding the naturally occurring "ARQ" polymorphic variant (Ala[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\PrPARQ.Scer\UAS flies are exposed to (fed) ovine scrapie prion inocula during the larval stage in order to model prion disease. These flies show a significant and progressive reduction in locomotor activity compared to controls, though survival time is unaffected.
Unlike controls, flies expressing Oari\PrPARQ.UAS under the control of Scer\GAL4elav-C155 and infected at the larval stage with Pa[[59]] prions support fly-to-mouse prion propagation. Flies expressing Oari\PrPVRQ.UAS under the control of Scer\GAL4elav-C155 and infected with Pa[[59]] prions show a progressive decrease in climbing ability, which is much more severe than in infected controls.
The expression of Oari\PrPARQ.Scer\UAS under the control of Scer\GAL4elav-C155 results in decreases in both adult lifespan and adult locomotor ability as compared to controls.
Adults expressing Zzzz\PrPARQ.Scer\UAS under the control of Scer\GAL4elav-C155 and exposed to ARQ/ARQ scrapie-infected sheep brain homogenate at the larval stage by oral exposure show a rapid decline in locomotor activity with age compared to animals expressing Zzzz\PrPARQ.Scer\UAS under the control of Scer\GAL4elav-C155 and exposed to control (scrapie-negative) ARQ/ARQ sheep brain material. By 40 days of age the flies exposed to scrapie prions are almost moribund.