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Publication : Visualization of prion infection in transgenic mice expressing green fluorescent protein-tagged prion protein.

First Author  Barmada SJ Year  2005
Journal  J Neurosci Volume  25
Issue  24 Pages  5824-32
PubMed ID  15958749 Mgi Jnum  J:346493
Mgi Id  MGI:7616529 Doi  10.1523/JNEUROSCI.1192-05.2005
Citation  Barmada SJ, et al. (2005) Visualization of prion infection in transgenic mice expressing green fluorescent protein-tagged prion protein. J Neurosci 25(24):5824-32
abstractText  Tg(PrP-EGFP) mice express an enhanced green fluorescent protein (EGFP)-tagged version of the prion protein (PrP) that behaves like endogenous PrP in terms of its posttranslational processing, anatomical localization, and functional activity. In this study, we describe experiments in which Tg(PrP-EGFP) mice were inoculated intracerebrally with scrapie prions. Although PrP-EGFP was incapable of sustaining prion infection in Tg(PrP-EGFP)/Prn-p(0/0) mice, it acted as a dominant-negative inhibitor that bound to, and fluorescently marked, deposits of PrPSc generated from endogenous PrP in Tg(PrP-EGFP)/Prn-p(+/+) mice. Scrapie infection of these latter animals caused a progressive accumulation of fluorescent PrP-EGFP aggregates in neuropil, axons, and prominently in the Golgi apparatus of neurons. Our results provide an entirely new picture of PrPSc localization during the course of prion infection, and they identify for the first time intracellular sites of PrPSc formation that are not well visualized with conventional immunohistochemical techniques.
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