129 OLA MICE CARRYING A NULL MUTATION IN PRP THAT ABOLISHES MESSENGER-RNA PRODUCTION ARE DEVELOPMENTALLY NORMAL/

The neural membrane glycoprotein PrP is implicated in the pathogenesis of the transmissible spongiform encephalopathies; however, the normal function of PrP and its precise role in disease are not understood. R ecently, gene targeting has been used to produce mice with neo/PrP fus ion transcripts, but no detectable PrP protein in the brain (I). Here we report the use of a different targeting strategy, to produce inbred mice with a complete absence of both PrP protein and mRNA sequences. At 7 mo of age, these mice show no overt phenotypic abnormalities desp ite the normal high levels of expression of PrP during mouse developme nt. The mice are being used in experiments designed to address the rol e of PrP in the pathogenesis of scrapie and the replication of infecti vity.