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Is PrPSc a reliable diagnostic marker for TSE infectivity
Reference
BBS/E/I/00001155
Principal Investigator / Supervisor
Dr Rona Barron
Co-Investigators /
Co-Supervisors
Institution
The Pirbright Institute
Department
The Pirbright Institute Department
Funding type
Research
Value (£)
13,724
Status
Completed
Type
Institute Project
Start date
01/10/2004
End date
30/09/2007
Duration
36 months
Abstract
The presence of scrapie and BSE in the UK and Europe, and concerns over the possible transmission of BSE to sheep necessitate the continued surveillance for these diseases. Diagnostic tests must be reliable, and capable of detecting all forms of disease. The presence of an abnormal form of the host prion protein (PrPSc) in brain tissue is currently used as a marker for scrapie and BSE, and immunodiagnostic techniques rely on the measurement of PrPSc to assess the infectious status of an animal. However it has been found in laboratory models that Transmissible Spongiform Encephalopathy (TSE) infectivity can be present without detectable levels of PrPSc, therefore current diagnostic techniques may fail to detect TSE infected animals. Moreover several sheep have recently tested positive in the Bio-Rad TeSeE diagnostic assay that cannot be confirmed by other immunodiagnostic methods.These results suggest that the different diagnostic assay systems may be detecting different forms of PrP and the relationship between these forms of PrP and infectivity is not clear. It is important to re-assess the validity of using PrPSc as a diagnostic marker for TSE disease. We have identified two specific mouse models of TSE disease but show little or no proteinase K (PK) resistant PrP in terminal brain tissue. These models contain moderate to high levels of TSE infectivity, despite the apparent absence of appreciable levels of PrPSc, and comparisons with well characterised mouse models of TSE disease show no correlation between the levels of PrPSc and infectivity. Mice from these models contain TSE infectivity and can be used to test current diagnostic methods, and analyse the nature of infectivity. The results will determine the validity of using PrPSc as a definitive marker associated with infectivity for diagnostic testing, and whether it is justifiable to base decisions on the infectious status of a tissue on the presence or absence of PrPSc.
Summary
unavailable
Committee
Closed Committee - Agri-food (AF)
Research Topics
X – not assigned to a current Research Topic
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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