The Genomic Identity of Different Strains of Mouse Scrapie Is Expressed in Hamsters and Preserved on Reisolation in Mice

Abstract

SUMMARY263K is the most widely used strain of agent in scrapie research because it produces very short incubation periods in golden hamsters and exceptionally high infectivity titres in clinically affected brain. 263K is also remarkable in having a very low pathogenicity for mice. Evidence is presented that 263K originated as a mutant that was strongly selected on passage in hamsters. Seven new passage lines have been established in hamsters using well characterized strains of mouse scrapie representing the 'drowsy goat' and SSBP/1 families of scrapie strains, and one natural scrapie source. Considerable differences between scrapie strains were found in hamsters using incubation period criteria alone. There was evidence that the parent strain of 263K might be 79V or a strain like it in the 'drowsy goat' family. Four of the hamster passage lines were established from scrapie strains that had been cloned in mice. Reisolates in mice were compared with original strains. By the criteria used, two of the reisolates were the same as the original strains. Two others were mutants with incubation periods longer than those of their parental strains but the mutants were different from one another. It is concluded that passage between mice and hamsters can select mutants that would otherwise be lost but there is also clear evidence that the genotypic identity of some scrapie strains is preserved on passage between different host species. These findings are important in the search for the putative nucleic acid genome of the scrapie agent.

Two Creutzfeldt–Jakob disease agents reproduce prion protein-independent identities in cell cultures

“…Other strains have also bred true after extended passages in a foreign species (26). Moreover, the epidemic U.K. bovine spongiform encephalopathy agent from cows, humans, domestic cats, nyala, and kudu all reproduce the same bovine spongiform encephalopathy-specific lesion profile and transmission characteristics in congenic mice, i.e., the bovine spongiform encephalopathy agent also maintains host independent characteristics (27).…”

Variation in the characteristics of 10 mouse-passaged scrapie lines derived from five scrapie-positive sheep

“…It is possible that scrapie agent populations with different properties develop in sheep during the long incubation period and that the host fails to provide selective advantages for any particular population. When material is then passaged into genetically diverse hosts different selective pressures permit the appearance of distinctive populations of agent (Kimberlin & Walker, 1977, 1978Kimberlin et al, 1987Kimberlin et al, , 1989Dickinson & Outram, 1983 Kimberlin, 1982), in which the informational molecule is an agent-associated nucleic acid. In the prion (Prusiner, 1982(Prusiner, , 1987Prusiner et al, 1987) or modified host protein (Bolton & Bendheim, 1988) hypothesis, the agent is composed exclusively of a protease-resistant, host-coded protein termed PrP.…”

“…A series of 10 passage lines was established from five scrapie-positive sheep, with each sheep providing a line initiated in s7s7 mice and a line initiated in p7p7 mice. Passages from a single host into different species (Kimberlin & Walker, 1977, 1978Kimberlin et al, 1987Kimberlin et al, , 1989, or into mice with different Sinc genotypes (Dickinson & Outram, 1983), often yield scrapie agent populations with different characteristics. The passage lines were analysed for two parameters that are under genetic control of host and agent: incubation periods in mice of different Sinc genotypes (Dickinson & Meikle, 1971) and increase in weight during the preclinical phase of disease (Outram, 1972;Carp et al, 1984Carp et al, , 1989cKim et al, 1987 b).…”

Demonstration of scrapie strain diversity in infected PC12 cells

“…In mice, more than 20 scrapie strains have been identified based on differences in biological, biochemical and histopathological parameters Kascsak et al, 1985Kascsak et al, , 1986Kascsak et al, , 1991. More recently, the establishment of distinct scrapie strains in hamsters has also been described (Kimberlin et al, 1987(Kimberlin et al, , 1989Carp et al, 1990;. However, the existence of scrapie strains in in vitro cell systems has not been demonstrated.…”