Sheep and goats: natural and experimental TSEs and factors influencing incidence of disease.

The major factor influencing incidence of disease following challenge with transmissible spongiform encephalopathies (TSEs) in sheep is the allotype at amino acid numbers 136, 154 and 171 of the PrP protein. There are at least two groups of TSEs, one which targets the amino acid encoded at position 136 and the other which is more influenced by the amino acid at codon 171. Within these groups of TSE types, there may additionally be sub-types, as resistance to some, but not all, "136-type" TSEs can also be affected by the amino acid at codon 154. In goats, there are also PrP polymorphisms which apparently influence incubation period of TSE disease, however, this has not found to be true for cattle and BSE incidence. Sheep PrP amino acid codons 136, 154 and 171 do not explain everything about, for example, natural scrapie occurrence in sheep flocks, and attention is now turning to the flanking regions of the PrP gene looking for sequence differences in gene expression control motifs which may also have an influence on disease development. The sheep PrP gene produces two mRNAs in peripheral tissues, the result of alternative polyadenylation in the 3' untranslated region of the gene. Results from transfection assays of murine neuroblastoma cells with constructs expressing different regions of ovine PrP mRNA have revealed the presence of sequences in the 3' untranslated region that modulate protein synthesis and have therefore the potential to affect disease progression.