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Citation
Choi, J.K., Jeon, Y.C., Lee, D.W., Oh, J.M., Lee, H.P., Jeong, B.H., Carp, R.I., Koh, Y.H., Kim, Y.S. (2010). A Drosophila model of GSS syndrome suggests defects in active zones are responsible for pathogenesis of GSS syndrome.  Hum. Mol. Genet. 19(22): 4474--4489.
FlyBase ID
FBrf0212151
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC3298851 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Hum. Mol. Genet.
    Title
    Human Molecular Genetics
    Publication Year
    1992-
    ISBN/ISSN
    0964-6906
    Data From Reference
    Alleles (11)
    Genes (8)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (3)
    Experimental Tools (3)
    Transgenic Constructs (8)