Identification of two prion protein regions that modify scrapie incubation time.
A series of prion transmission experiments was performed in transgenic (Tg) mice expressing either wild-type, chimeric, or truncated prion protein (PrP) molecules. Following inoculation with Rocky Mountain Laboratory (RML) murine prions, scrapie incubation times for Tg(MoPrP)4053, Tg(MHM2)294/Prnp(0/0), and Tg(MoPrP, Delta23-88)9949/Prnp(0/0) mice were approximately 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(Delta23-88)(RML) prions, excluding the possibility that sequence-dependent transmission barriers could account for the observed differences. Tg(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 through 111) both influence the inherent efficiency of prion propagation.
Supattapone
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S
Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94143, USA.
Muramoto
T
T
Legname
G
G
Mehlhorn
I
I
Cohen
F E
FE
DeArmond
S J
SJ
Prusiner
S B
SB
Scott
M R
MR
D000818:Animals; D000939:Epitopes; D051379:Mice; D008822:Mice, Transgenic; D011328:Prions / Q000737:chemistry / Q000502:physiology*; D012608:Scrapie / Q000209:etiology*; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013997:Time Factors
D000939:Epitopes; D011328:Prions