Award details

Pathogenesis & epidemiology of TSE in sheep

Reference	BBS/E/A/00001656
Principal Investigator / Supervisor	Professor Nora Hunter
Co-Investigators / Co-Supervisors	Dr James Foster
Institution	The Roslin Institute
Department	The Roslin Institute Department
Funding type	Research
Value (£)	350,772
Status	Completed
Type	Institute Project
Start date	01/04/2007
End date	31/03/2012
Duration	60 months

Abstract

Despite the recent advances in the understanding of genetics and pathogenesis of TSEs in sheep, the route(s) by which TSEs transmit naturally between sheep remains unknown. There is a clear link between PrP genotype and differences in susceptibility/resistances to experimental scrapie and BSE and natural TSEs in sheep, however the controlling mechanisms at the cellular and molecular level are not understood. This research programme will use various approaches to address these issues including detailed analysis of PrPc expression patterns in different genotypes of sheep, demonstrating age-related susceptibility differences and how these may be related to gut physiology changes, and establishing which cells are involved in maternal transmission of scrapie in utero, and/or during the first 24 hours of a lamb¿s life. The NPU Cheviot flock has endemic natural scrapie and has recently been found also to have atypical scrapie, which gives us a unique chance to understand the epidemiology, pathogenesis and transmission of both diseases in comparison with experimental strains. The NPU flock has detailed records going back to its creation in the 1960s and has produced a unique archive of tissue samples available for PrP protein and genotype studies with newer technologies as they become available. The flock also represents an opportunity to assess diagnostics and to test therapies such as pentosan polysulphate. Finally this project will include strain transmission studies and titrations in conventional and transgenic mice expressing sheep gene PrP alleles to allow us to demonstrate whether genotype and PrPc levels are associated with infectivity titre changes. PrPsc glycoform and IHC analyses are carried out on all animals and transmissions, to identify the infecting TSE strain and provide body tissue patterns of PrPsc expression which allow us to describe pathogenesis in detail.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
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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