GFP-tagged mutant prion protein forms intra-axonal aggregates in transgenic mice.
A nine-octapeptide insertional mutation in the prion protein (PrP) causes a fatal neurodegenerative disorder in both humans and transgenic mice. To determine the precise cellular localization of this mutant PrP (designated PG14), we have generated transgenic mice expressing PG14-EGFP, a fluorescent fusion protein that can be directly visualized in vivo. Tg(PG14-EGFP) mice develop an ataxic neurological illness characterized by astrogliosis, PrP aggregation, and accumulation of a partially protease-resistant form of the mutant PrP. Strikingly, PG14-EGFP forms numerous fluorescent aggregates in the neuropil and white matter of multiple brain regions. These aggregates are particularly prominent along axonal tracts in both brain and peripheral nerve, and similar intracellular deposits are visible along the processes of cultured neurons. Our results reveal intra-axonal aggregates of a mutant PrP, which could contribute to the pathogenesis of familial prion disease by disrupting axonal transport.
Medrano
Andrea Z
AZ
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Barmada
Sami J
SJ
Biasini
Emiliano
E
Harris
David A
DA
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D049452:Green Fluorescent Proteins; D047468:Immunoprecipitation; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D049408:Luminescent Agents; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D050505:Mutant Proteins / Q000378:metabolism*; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D049408:Luminescent Agents; D050505:Mutant Proteins; D011328:Prions; D049452:Green Fluorescent Proteins