There are many distinct strains of scrapie agent, identified by their relative incubation periods and quantitative and qualitative neuropathological properties in inbred mice of particular genotypes. When serially passaged under specified conditions of mouse strain, route of infection and dose of infectivity these properties are stable. However, they may change in a predictable manner if the passage strategy is altered.
The scrapie strain 87A shows what has previously been defined as Class III stability; it is stable when passaged at low dose in C57BL mice, but often suddenly changes its properties in the course of a single passage if high doses are used, always resulting in the same new strain. The latter, designated 7D, has shorter incubation periods and more extensive pathology than 87A, properties which are subsequently stable on serial passage even at high dose. This phenomenon has been seen repeatedly using scrapie isolates from six different natural cases in five different breeds of sheep. These isolates are closely similar in all their properties, showing them to be independent isolations of the 87A strain; there have been no isolations of 87A in which the phenomenon did not occur. On the other hand, none of the many other scrapie strains used in the same laboratory have shown this change. 87A brain samples consistently behave as if they contain 87A together with a smaller amount of 7D. This is so even after 87A has previously been passaged at high dilution, well beyond the limiting dilution for 7D, a procedure which would eliminate any minor agent strain originally present in the isolate. Therefore it is highly likely that the 7D in tissues of mice infected with 87A is generated de novo at each passage by mutational change from 87A during the incubation period. The established fact that many different strains exist and the considerable evidence that mutation can occur lead to the conclusion that scrapie agent has its own independently replicating genome.
BruceM. E., DickinsonA. G.1979; Biological stability of different classes of scrapie agent. In Slow Transmissible Diseases of the Nervous System2 pp. 71–86PrusinerS. B., HadlowW. J. Edited by New York: Academic Press;
BruceM. E., FraserH.1982; Focal and asymmetrical vacuolar lesions in the brains of mice infected with certain strains of scrapie. Acta neuropathologica 58:133–140
BruceM. E., DickinsonA. G., FraserH.1976; Cerebral amyloidosis in scrapie in the mouse: effect of agent strain and mouse genotype. Neuropathology and Applied Neurobiology 2:471–478
DickinsonA. G., FraserH.1977; Scrapie pathogenesis in inbred mice: an assessment of host control and response involving many strains of agent. In Slow Virus Infections of the Central Nervous System pp. 3–14Ter MeulenV., KatzM. Edited by New York: Springer-Verlag;
DickinsonA. G., OutramG. w.1979; The scrapie replication-site hypothesis and its implications for pathogenesis. In Slow Transmissible Diseases of the Nervous System2 pp. 13–31PrusinerS. B., HadlowW. J. Edited by New York: Academic Press;
DickinsonA. G., OutramG. w.1983; Operational limitations in the characterisation of the infective units of scrapie. In Virus Non-conventionnels et Affections du Systeme Nerveux Central pp. 3–16CourtL. A., CathalaF. Edited by Paris: Masson;
DickinsonA.G, MeikleV. M. H., FraserH.1968; Identification of a gene which controls the incubation period of some strains of scrapie in mice. Journal of Comparative Pathology 78:293–299
DickinsonA. G., Meiklev. M. H., FraserH.1969; Genetical control of the concentration of ME7 scrapie agent in the brain of mice. Journal of Comparative Pathology 79:15–22
DickinsonA. G., FraserH., McconnellI., OutramG. W., SalesD. I., TaylorD. M.1975; Exttaneural competition between different scrapie agents leading to loss of infectivity. Nature; London: 253556
DickinsonA. G., BruceM. E., OutramG. w., KimberlinR. H.1984; Scrapie strain differences: the implication of stability and mutation. In Proceedings of Workshop on Slow Transmissible Diseases pp. 105–118 Tokyo: Japanese Ministry of Health and Welfare;
FraserH.1976; The pathology of natural and experimental scrapie. In Slow Virus Diseases of Animals and Man pp. 267–305KimberlinR. H. Edited by Amsterdam: North-Holland;
FraserH., DickinsonA. G.1973; Scrapie in mice: agent-strain differences in the distribution and intensity of grey matter vacuolation. Journal of Comparative Pathology 83:29–40
GermanT. L., MarshR. F.1983; The scrapie agent: a unique self-replicating pathogen. In Progress in Molecular and Subcellular Biology8 pp. 111–121HahnF. E. Edited by Berlin: Springer-Verlag;
KimberlinR. H., WalkerC. A.1978; Evidence that the transmission of one source of scrapie agent to hamsters involves separation of agent strains from a mixture. Journal of General Virology 39:487–496
KimberlinR. H., WalkerC. A., MillsonG. C., TaylorD. M., RobertsonP. A., TomlinsonA. H., DickinsonA. G.1983; Disinfection studies with two strains of mouse-passaged scrapie agent. Journal of the Neurological Sciences 59:355–369
ZlotnikI., RennieJ. C.1963; Further observations on the experimental transmission of scrapie from sheep and goats to laboratory mice. Journal of Comparative Pathology 73:150–162