2010 -- Generating a Prion with Bacterially Expressed Recombinant Prion Protein
The prion hypothesis posits that a misfolded form of prion protein (PrP) is responsible for the
infectivity of prion disease. Using recombinant murine PrP purified from Escherichia coli, we
created a recombinant prion with the hallmarks of the pathogenic PrP isoform: aggregated,
protease-resistant, and self-perpetuating. After intracerebral injection of the recombinant
prion, wild-type mice developed neurological signs in ~130 days and reached the terminal
stage of disease in ~150 days. Characterization of diseased mice revealed classic
neuropathology of prion disease, the presence of protease-resistant PrP, and the capability
of serially transmitting the disease, confirming that these mice succumbed to prion disease.
Thus, as postulated by the prion hypothesis, the infectivity in mammalian prion disease
results from an altered conformation of PrP.
Science DOI: 10.1126/science.1183748
http://www.sciencemag.org/cgi/content/abstract/science.1183748