The cellular prion protein (PrP C), a membrane glycoprotein anchored to the outer surface of neurons, lymphocytes and other cells, is associated directly with the pathogenesis of the transmissible spongiform encephalopathies (TSEs) occurring mainly in humans, cattle, sheep and goats. Although mice lacking PrP C develop and reproduce normally and are resistant to scrapie infection, large animals lacking PrP C , especially those species in which TSE occurs naturally, are currently not available. Here, five live PRNP +/" goats cloned by gene targeting are reported. Detailed RNA-transcription and protein-expression analysis of one PRNP +/" goat showed that one allele of the caprine PRNP gene had been disrupted functionally. No gross abnormal development or behaviour could be seen in these PRNP +/" goats up to at least 3 months of age. These heterozygous PRNP +/" goats are ready to be used in producing homozygous PRNP "/" goats in which no PrP C should be expressed.
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