Scrapie transgenic studies

The first evidence to suggest that the primary sequence of PrP could profoundly influence TSE species barriers came from studies utilizing the strong barrier to infection that exists between hamsters and mice. Although mice are fully susceptible to mouse scrapie, they are resistant to infection with a particular strain of hamster scrapie. Mice infected with hamster scrapie do not become clinically ill within the lifetime of the animal even though it appears that infectivity can be sequestered in these animals (Race and Chesebro, 1998). However, transgenic mice that overexpressed hamster PrP-sen were fully susceptible to hamster scrapie (Scott et al, 1989). Subsequent studies demonstrated that the hamster/mouse species barrier could be crossed even when hamster PrP-sen expression was restricted to neurons (Race et al, 1995) or astrocytes (Raeber et al, 1997), but not T-cells or hepatocytes (Raeber et al,... 

The caveat with all of the current transgenic mouse models of familial TSE is that none precisely replicate the human disease. Almost all of them are dependent on transgenic mouse studies that involve both overexpression and random insertion of the transgene. In fact, when a single copy of a PrP mutant associated with GSS (proline to leucine at 102) is specifically substituted into the PrP gene locus, no spontaneous neurodegenerative disease is observed (Manson et al, 1999). Rather, an increased resistance to infection with scrapie is found (Manson et al,... 

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