Since 2002, the national scrapie surveillance scheme has examined over 90,000 sheep brain stem samples using the Bio-Rad TeSe rapid test for detection of abnormal PrP. Seventy-nine of these samples could not be confirmed by either Western blotting or immunohistochemistry (IHC), at the level of the obex, and so remain unclassified with respect to EU scrapie status. Follow-up biochemical studies have shown that in these cases the PrP detected as positive in the Bio-Rad test is either an excess of normal PrPC or a proteinase K sensitive PrPSc. More recently, this has been correlated to IHC staining of the trigeminal nucleus with the PrP monoclonal antibody (mAb), 2G11. Most of these unclassified cases were in sheep carrying at least one ARR or AHQ PrP allele. As selection of these alleles is favoured by the National Scrapie Plan (NSP), it is important to evaluate if this rapid test is detecting false positive cases or if, for some reason, it can detect incipient infection before other statutory, post-mortem methods. The NSP is the keystone of Defra’s BSE in Sheep Contingency Plan and part of the Food Standards Agency’s strategy to minimise human exposure to BSE. If ARR or AHQ sheep can be naturally infected, and this is being detected by the Bio-Rad TeSE test, and by IHC with mAb 2G11, then modifications to the NSP may be required.
We propose to attempt transmission from a selection of these ARR and AHQ allele carriers, and from Bio-Rad TeSe test-negative controls, to conventional and transgenic mouse lines to establish whether or not they are carriers of infection.
This proposal is complimentary to the proposal from Dr. M. Simmons (VLA, Weybridge) which is aimed at assessing the transmissibility of these cases to sheep