Prion protein of 106 residues creates an artificial transmission barrier for prion replication in transgenic mice

A redacted prion protein (PrP) of 106 amino acids with two large deletions was expressed in transgenic (Tg) mice deficient for wild-type (wt) PrP (Prn p(0/0)) and supported prion propagation. RML prions containing full-length PrPSc produced disease in Tg(PrP106)Prnp(0/0) mice after similar to 300 day s, while transmission of RML106 prions containing PrP(Sc)106 created diseas e in Tg(PrP106) Prnp(0/0) mice after only similar to 65 days on repeated pa ssage. This artificial transmission barrier for the passage of RML prions w as diminished by the coexpression of wt MoPrPC in Tg(PrP106)Prnp(+/0) mice that developed scrapie in similar to 165 days, suggesting that wt MoPrP act s in trans to accelerate replication of RML106 prions. Purified PrP(Sc)106 was protease resistant, formed filaments, and was insoluble in nondenaturin g detergents. The unique features of RML106 prions offer insights into the mechanism of prion replication, and the small size of PrP(Sc)106 should fac ilitate structural analysis.