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Molecular analysis of PrP gene variation in various mammalian species to deduce PrP sequence motifs with a role in TSE's

Reference	BBS/E/A/00001652
Principal Investigator / Supervisor	Dr Wilfred Goldmann
Co-Investigators / Co-Supervisors
Institution	The Roslin Institute
Department	The Roslin Institute Department
Funding type	Research
Value (£)	112,746
Status	Completed
Type	Institute Project
Start date	01/04/2007
End date	31/03/2010
Duration	36 months

Abstract

Knowledge of the differences between ovine and murine PrP gene expression is limited and not yet sufficient to model sheep specific regulatory processes in transgenic mice. It is therefore necessary to continue our studies on sheep promoter sequence motifs that control PrP expression spatially and temporally. Transcription regulators such as E4BP4 and YY1 have been shown to interact with the ovine PrP promoter and their role in PrP control have been tested in N2a culture with luciferase reporter gene analysis. Comparisons of PrP mRNA expression patterns between ovine and other species eg. deer have been used to select crucial elements of PrP regulation. PrP expression in species that can be infected with TSEs (eg. ruminants, feline species) will be compared with species that have not been infected (eg. canine species). Sheep susceptible to classical scrapie (genotype LL141, RR154) have been compared in PrP expression to sheep that are susceptible to atypical scrapie (FF141, HH154). Future studies could then use this information to insert a consensus sheep PrP promoter into transgenic mouse models to mimic sheep expression pattern. It is not understood why in SSBP/1 scrapie challenges susceptibility differs between ARQ/ARQ Suffolks, NPU Cheviots and their crossbred offspring. We are currently characterising molecular markers (SNPs) in the UTR and promoter that associate with susceptibility and/or incubation period in models of classical and atypical scrapie.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Animal Health, Neuroscience and Behaviour, TSEs (transmissible spongiform encephalopathies)
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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