title: A Drosophila model of GSS syndrome suggests defects in active zones are responsible for pathogenesis of GSS syndrome.
abstract: We have established a Drosophila model of Gerstmann-Sträussler-Scheinker (GSS) syndrome by expressing mouse prion protein (PrP) having leucine substitution at residue 101 (MoPrP(P101L)). Flies expressing MoPrP(P101L), but not wild-type MoPrP (MoPrP(3F4)), showed severe defects in climbing ability and early death. Expressed MoPrP(P101L) in Drosophila was differentially glycosylated, localized at the synaptic terminals and mainly present as deposits in adult brains. We found that behavioral defects and early death of MoPrP(P101L) flies were not due to Caspase 3-dependent programmed cell death signaling. In addition, we found that Type 1 glutamatergic synaptic boutons in larval neuromuscular junctions of MoPrP(P101L) flies showed significantly increased numbers of satellite synaptic boutons. Furthermore, the amount of Bruchpilot and Discs large in MoPrP(P101L) flies was significantly reduced. Brains from scrapie-infected mice showed significantly decreased ELKS, an active zone matrix marker compared with those of age-matched control mice. Thus, altered active zone structures at the molecular level may be involved in the pathogenesis of GSS syndrome in Drosophila and scrapie-infected mice.
authors.affiliation: Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyangdong Dongangu, Anyang, Gyeonggi-Do, Republic of Korea.
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Choi
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Jeon
authors.forename: Dae-Weon
authors.initials: DW
authors.lastname: Lee
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Oh
authors.forename: Hyun-Pil
authors.initials: HP
authors.lastname: Lee
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Jeong
authors.forename: Richard I
authors.initials: RI
authors.lastname: Carp
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Koh
authors.forename: Yong-Sun
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004330:Drosophila; D005260:Female; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics* / Q000378:metabolism
chemical_list: D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse