Generating a Prion with Bacterially Expressed Recombinant Prion Protein
Fei Wang,1,* Xinhe Wang,1,* Chong-Gang Yuan,2 Jiyan Ma1,2,
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.
1 Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, OH 43210, USA.
2 School of Life Science, East China Normal University, Shanghai 200062, China.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: ma.131@osu.edu