Related Experiment Video
Updated: Aug 30, 2026
Monitoring Immune Cells Trafficking Fluorescent Prion Rods Hours after Intraperitoneal Infection
Published on: November 19, 2010
Transmission of murine scrapie to P101L transgenic mice
Rona M Barron1, Val Thomson1, Declan King1
1Neuropathogenesis Unit, Institute for Animal Health, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK.
Abstract:
The PrP protein is central to the transmissible spongiform encephalopathies (TSEs), and the amino acid sequence of this protein in the host can influence both incubation time of disease and targeting of disease pathology. The N terminus of murine PrP has been proposed to be important in the replication of TSE agents, as mutations or deletions in that region can alter the efficiency of agent replication. To address this hypothesis and to investigate the mechanisms by which host PrP sequence controls the outcome of disease, we have assessed the influence of a single amino acid alteration in the N-terminal region of murine PrP (P101L) on the transmission of TSE agents between mice. Mice homozygous for the mutation (101LL) were inoculated with TSE strains 139A and 79A derived from mice carrying a Prnp(a) allele, and 79V and 301V derived from mice carrying a Prnp(b) allele. Incubation times in 101LL mice were extended with all four strains of agent when compared with those in the corresponding mouse genotype from which the infectivity was derived. However, the degree to which the incubation period was increased showed considerable variation between each strain of agent. Moreover, the presence of this single amino acid alteration resulted in a 70 day reduction in incubation time of the 301V strain in Prnp(a) mice. The effect of the 101L mutation on murine scrapie incubation time appears therefore to be strain specific.
Insights
A single amino acid change in the prion protein (PrP) N-terminus influences transmissible spongiform encephalopathy (TSE) agent replication and disease progression in mice. This P101L mutation affects incubation times, demonstrating strain-specific impacts on TSE pathogenesis.
Area of Science:
- Neuroscience
- Molecular Biology
- Prion Biology
Background:
- The prion protein (PrP) is central to transmissible spongiform encephalopathies (TSEs).
- Host PrP amino acid sequence influences disease incubation and pathology.
- The N-terminus of PrP is implicated in TSE agent replication.
Purpose of the Study:
- To investigate the role of a single amino acid alteration (P101L) in the N-terminal region of murine PrP.
- To assess the influence of the P101L mutation on TSE agent replication and disease outcome.
- To understand how host PrP sequence controls TSE pathogenesis.
Main Methods:
- Mice homozygous for the P101L mutation (101LL) were generated.
- 101LL mice were inoculated with four different TSE strains (139A, 79A, 79V, 301V).
- Incubation times were compared to control mice with different Prnp alleles.
Main Results:
- The P101L mutation extended incubation times for all four TSE strains in 101LL mice compared to controls.
- The degree of incubation time extension varied significantly between different TSE strains.
- In Prnp(a) mice, the 101L mutation reduced incubation time for the 301V strain by 70 days.
Conclusions:
- The P101L mutation in murine PrP has a significant impact on TSE agent replication and incubation periods.
- The effect of the P101L mutation is strain-specific, highlighting the complex interplay between host PrP and TSE agents.
- This study provides insights into the mechanisms by which host PrP sequence modulates TSE disease progression.
