| Summary: | To investigate the role of PrP in conferring susceptibility to transmissible spongiform encephalopathies and furthermore to investigate the effect of restricted hamster PrP expression on the susceptibility to the hamster scrapie agent, we attempted to generate transgenic mice by using the hamster PrP open reading frame only, linked to appropriate regulatory 5' flanking sequences of brain specific genes. Although correct mRNA expression was achieved in some of the transgenic lines generated, problems were encountered with PrP protein production, indicating translational control of PrP. It was postulated that other PrP sequences could be important for mRNA regulation and efficient translation. The examination of the role of untranslated regions of the PrP mRNA was considered of major importance. The effect of 5' and 3' untranslated sequences of hamster PrP was tested on the translation of both PrP and lacZ. The effect of other regulatory sequences (a generic intron and an altered translation of initiation consensus sequence) was also investigated. However, none of the sequences tested appeared to have a significant effect on either PrP or lacZ translation efficiencies.
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