Refined Transgenic Mouse Models Which Recapitulate the Natural Features of Chronic Wasting Disease With Rapid Prion Disease Onsets.

Abstract

Prions are infectious, host encoded proteins which cause fatal neurodegenerative diseases of mammals. Seminal studies showed that overexpression of cervid prion protein (PrP) transgenes eliminated the transmission barrier to chronic wasting disease (CWD) prions in mice. Subsequent models which controlled expression from targeted alleles of the mouse PrP gene provided an improved framework for reproducing additional aspects of natural CWD. Here, we generated mice which combine the advantages of transgene overexpression with refinements afforded by gene targeting. Disease was characterized by accelerated onsets following peripheral or intracerebral challenges and by faithful recapitulation of native CWD strain properties including lymphotropic replication.