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        Transgenic Studies of Prion Diseases

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        This chapter reviews studies that involve the manipulation of prion protein (PrP) genes by transgenesis in mice. These consist of two approaches: PrP gene knockout and gene replacement using homologous recombination in embryonic stem cells; and microinjection of transgenes into fertilized embryos. These studies have provided important insights into the pathogenesis of prion diseases including the molecular basis of prion strains and species barriers. Transgenic approaches have also provided important information about the mechanism by which human prion diseases can be both genetic and infectious. Despite these advances, our understanding of these unique pathogens is far from complete. Transgenic approaches will doubtless remain the cornerstone of investigations into the prion diseases, and will be important in the development of therapeutic agents in coming years.
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