An investigation of TSE resistance mechanisms by genetic analysis of PrP binding protein genes

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The PrP protein allotypes are crucial modulators of TSE pathogenesis. Amino acid changes in PrP can mean the difference between susceptibility and resistance but the mechanism though which these effects are enacted is not understood. PrP-binding protein (PrPbp) genes, ie. NCAM or laminin receptor are prime candidates to explore the causal relationship between PrP alleles and phenotypes such as neuronal cell death. We propose to investigate PrPbps in our well-understood sheep scrapie models, by initiating an analysis of their gene sequences, polymorphisms and expression patterns in scrapie-relevant tissues. Co-immunoprecipitations will provide detailed analysis of the molecular interaction between allotypes of PrP and its protein ligands.