263K 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.


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