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Gene targeted transgenic mice expressing human PrP as models for studying CJD

ReferenceBBS/E/I/00000985
Principal Investigator / Supervisor Professor Jean Manson
Co-Investigators /
Co-Supervisors
Institution The Pirbright Institute
DepartmentThe Pirbright Institute Department
Funding typeResearch
Value (£) 2,668
StatusCompleted
TypeInstitute Project
Start date 01/04/2003
End date 31/03/2008
Duration60 months

Abstract

We have produced transgenic mice in which the endogenous murine PrP gene has been altered by gene targeting to replace the murine PrP coding region with that of human PrP. One line encodes 129MM the other 129VV. This proposal aims to assess potential of these mice as models to study CJD, strains of TSE in humans and the influence of the 129 polymorphism in disease susceptibility. Mice will be inoculated with brain material which ahs been prepared in a WHO collaborative study as an International Reference Material for Diagnosis and Study of TSEs. Five different brains have been prepared and aliquoted at NIBSC, two sporadic CJD, one variant CJD and one non-CJD control all from 129MM individuals and one sCJD from a 129M129V individual. Material from a sCJD individual carrying a PrP gene encoding V129V129 (available from the CJD Surveillance Unit) also be used in this study. For each successful transmission, strain typing, PrP deposition and PrPSc analysis will be carried out and compared with that in wild type mice. Having established which lines are susceptible to which agents, these will be used to titre the infectivity in each brain and compare the susceptibility of the transgenic mice to that of wild type mice.

Summary

unavailable
Committee Closed Committee - Animal Sciences (AS)
Research TopicsX – not assigned to a current Research Topic
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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