Identification of two prion protein regions that modify scrapie incubationtime

A series of prion transmission experiments aas performed in transgenic (Tg) mice expressing either wild-type, chimeric, or truncated prion protein (Pr P) molecules. Following inoculation with Rocky Mountain Laboratory. (RML) m urine prions, scrapie incubation times far Tg(MoPrP)4053, Tg(MHM2)294/Prnp( 0/0), and Tg(MoPrP,Delta 23-88)9949/Prnp(0/0) mice were similar to 50, 120, and 160 days, respectively. Similar scrapie incubation times were obtained after inoculation of these lines of Tg mice with either MHM2(MHM2(RML)) or MoPrP(Delta 23-88)(RML) prions, excluding the possibility that sequence-de pendent transmission barriers could account for the observed differences. T g(MHM2)294/Prnp(0/0) mice displayed prolonged scrapie incubation times with four different strains of murine prions. These data provide evidence that the N terminus of MoPrP and the chimeric region of MHM2 PrP (residues 108 t hrough 111) both influence the inherent efficiency of prion propagation.