Transgenic Studies of the Species Barrier

Early experimental transmission studies of human prion diseases were mainly done in laboratory primates, in particular chimpanzees and squirrel monkeys (Brown et al, 1994). These early transmission studies had rather long incubation periods, were expensive, and attracted ethical concerns. Primary transmission of human prions to wild-type laboratory mice have also been fairly unsuccessful, with only occasional transmissions occurring and then at prolonged incubation periods, close to the natural life span of the mice. This difficulty in primary transmissions is the concept of species barrier (Pattison and Jones, 1968), the principal determinants of which appear to be degree of homology between the host and the inoculum (Prusiner et al, 1990) and the strain of disease agent. 

The preceding example based on wild-type prion protein is corroborated by results from transgenic mice producing artificial PrP . Scott et 

These authors inoculated a panel of human CJD cases into the Tg(HuPrP)152 transgenic mice and showed that one human CJD case, designated PDG170, resulted in eight of nine mice dying from neurological disease, with a mean incubation time of 297 days. 

The different susceptibilities observed between Tg(HuPrP)152 and Tg(MHu2M) mice led to the proposal of the existence of an additional protein, provisionally designated protein X, that might be necessary for susceptibility of the Tg(HuPrP) mice to human prions (Telling et al, 

The authors suggested that protein X might function as a molecular chaperone required in the formation of nascent PrP . Telling et al (1995) suggested that MoPrP produced by Tg(HuPrP)152 inhibited the conversion of HuPrP into PrP and that inhibition was abol- 

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