Human familial prion diseases have been extensively studied by modeling in mice expressing transgenes which express a human PrP mutation superimposed on a normal PrP sequence. PrP from several species including mouse, human, hamster, cow and bank vole have been generated. These models have recently been compared in an elegant review . Overall the results indicate that many of these models develop spontaneous disease with similarities to their human disease counterparts. Transmissible prion infectivity has been found in some, but not all, of these models [1, 12, 21, 49], suggesting that presence of prion infectivity is not absolutely required for the development of these signs of clinical neurological disease. One hypothesis suggests that PrP mutations linked to familial prion diseases can generate infectious prions in some afflicted patients ; however, an alternative possibility is that in other patients mutant PrP molecules might induce neurodegeneration by disruption of normal CNS functions without production of infectious prions [28, 50].