SUMMARYA previous paper (Kimberlin & Walker, 1977) described an experimental model of scrapie in hamsters in which the incubation period decreased progressively over the first 4 passages before becoming stable at the 5th and subsequent passes. Studies have been made of some of the agent strains present in brains taken from the 2nd, 3rd, 4th and 6th hamster passes. The results indicate the presence of at least two strains of agent at the 3rd passage level. One of these (43IK) is highly pathogenic for mice and the other (263K) has an extremely low pathogenicity for mice. However only one of these strains (263K) is present in hamster brain after the 6th serial passage. It is suggested that the 'adaptation' of scrapie to hamsters may involve the selection, from a mixture, of a single strain which is highly pathogenic for hamsters. The possibility of modification of the properties of agent strains on passage discussed.

The development of a short incubation model of scrapie (strain 263K), in golden hamsters has added impetus to the purification of the infectious agent. Our own attempts have been based on methods pioneered by Millson and developed by Prusiner. We present here results indicating that a purification factor of up to 10(4) with respect to protein may now be possible. Fractions from brain with high infectivity had a sedimentation range of 70-300S and contained an abundance of fibrils closely similar to the scrapie-associated fibrils (SAF) discovered by Merz et al.. Material of molecular weight (Mr) 26,000, which is probably protein, appears to be a major constituent of the fibrils. The association between infectivity and fibrils raises two possibilities: the fibrils are an infectious form of the scrapie agent or they are a pathological response to scrapie infection.

Scrapie‐associated fibrils (SAF) are unique structures characteristic of the group of unconventional slow infections which includes scrapie and Creutzfeldt‐Jakob disease. A major component of hamster fibrils has been described as a protease‐resistant glycoprotein with an apparent mol. wt of 27,000‐30,000 (PrP27‐30). However, we report here that if fibrils are prepared by procedures designed to minimise proteolysis the PrP proteins co‐purifying with hamster SAF have mol. wts of 33,000‐35,000 (PrP33‐35) and 26,000‐29,000 (PrP26‐29). We find a Lys‐Lys‐Arg‐Pro‐Lys sequence at the amino terminus of these SAF proteins, that is absent from PrP27‐30, and which has recently been predicted to be the N‐terminal sequence of the native PrP protein of uninfected brain. The major SAF protein (PrP33‐35) and its normal brain homologue are shown to have the same apparent mol. wt and ionic charge distribution by two‐dimensional gel analysis, silver staining and immunoblotting. These results support our view that PrP33‐35 and the normal brain PrP protein may have the same covalent structure, and that the PrP protein is recruited into these amyloid‐like SAF or into association with a non‐protein component of SAF by an irreversible event initiated directly or indirectly by scrapie infection.

SUMMARYRepeated passage of the ' Chandler' strain of scrapie in female golden hamsters using the intracerebral route of inoculation reduces the minimum incubation period to 60 days, about half of the minimum incubation period so far found in any of the mouse models of scrapie. The infectivity titres in brain in the clinical stage of the disease are considerably higher (> 8.0 -log10 LDs0 i.c. units]o.o5 g) than those found in mouse scrapie. The biological characteristics of this model of hamster scrapie are reported, including the effects on incubation period of route of inoculation, dose of agent, sex of hamster, ambient temperature (hibernation) and splenectomy. Some general and specific applications of this experimental model of scrapie are discussed.