Scrapie agent

Scrapie agents have been reported to cause obesity in mice, and the effect is dependent on the strain of scrapie. Relevance of the findings to humans has not been established. 

Scrapie is a neurodegenerative disease with a long incubation period, known to occur in sheep and goats, however, mice and other small rodents can be infected with it (Hunter, 1972). Certain scrapie strains induce obesity in 

Weight increase in scrapie-infected animals was observed as a preclinical manifestation as early as 1968 by Pattison and Jones (1968) and was followed by Outram and Markovits in 1972 and 1981, respectively (Markovits et al., 1981 Outram, 1972). 

Mice infected with certain strains of scrapie determine a significant increase in body weight in the preclinical phase of the disease (Carp et al., 1984). Regardless of the mouse strain, the scrapie strain ME7 injected in the hypothalamus-induced obesity (Carp et al., 1984, 1998 Kim et al., 1987, 1988). This effect was also observed for 22L scrapie strain injected in certain type of mice (Carp et al., 1984, 1998 Kim et al., 1987), but not for 139A (Carp et al., 1984, 1998 Kim et al., 1987, 1988) or 22A scrapie strains (Carp et al., 1984). 

ME7 injected in the hypothalamus, but not in cortex, induces obesity in C57NL mice. ME7 produced the same pattern of vacuolation in nine 

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Peyer s patch of scrapie- free lambs and lambs naturally and experimentally exposed to the scrapie agent. J Gen Virol 81(Pt 9) 2327-2337. 

Seidel B, Thomzig A, Buschmann A et al (2007) Scrapie agent (strain 263K) can transmit disease via the oral route after persistence in soil over years. PLoS ONE 2 e435... 

Bruce ME, Dickinson AG (1979) Biological stability of different classes of scrapie agent. In Prusiner SB, Hadlow WJ (eds) Slow transmissible diseases of the nervous system, vol 2. Academic Press, New York, pp 71-86... 

Bruce ME, Dickinson AG (1987) Biological evidence that the scrapie agent has an independent genome. J Gen Virol 68 79-89... 

Le Dur A, Beringue V, Andreoletti O, Reine F, Lai TL, Baron T, Bratberg B, Vilotte JL, Sarradin P, Benestad SL, Laude H (2005) A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes. Proc Natl Acad Sci USA 102 16031-16036... 

Der Trab ist auch eine Krankheit der Schaafe, und ist ansteckend. Sie schleppen sich lange, verzehren sich nach und nach, und zuletzt miissen sie sterben. These sentences are taken from an article published in 1759 [1] and describe two hallmarks of prion diseases or transmissible spongiform encephalopathies (TSEs, summarized in Table 1) The formation and transmission of an infectious particle and the invariably fatal course of these diseases. More than 200 years later a landmark discovery paved the way to study the pathogenesis of prion diseases at a molecular level. Prusiner and colleagues reported the identification of a protease-resistant protein in brain extracts, which co-purified with the infectious scrapie agent [18]. After the N-terminal amino acid sequence of the proteinase K (PK)-resistant core of the prion protein (PrP 27-30) was published in 1984 [19], two... 

Adjou, K.T., Demaimay, R., Deslys, J.P., Lasmezas, C.I., Beringue, V., Demart, S., Lam-oury, R, Seman, M., and Dormont, D. (1999). MS-8209, a water-soluble amphotericin B derivative, affects both scrapie agent replication and PrPres accumulation in Syrian hamster scrapie./. Gen. Virol. 80,1079-1085. 

Bendheim, PE. and Bolton, D.C. (1986). A 54-kDa normal cellular protein may be the precursor of the scrapie agent protease-resistant protein. Proc. Natl. Acad. Sci. U.S.A. 83,2214 2218. 

Caughey, B., Ernst, D., and Race, R. (1993a). Congo red inhibition of scrapie agent replication./ Virol. 67, 6210-6272. 

McKenzie, D., Kaczkowski, J., Marsh, R., and Aiken, J. (1994). Amphotericin B delays both scrapie agent replication and PrP-res accumulation early in infection./. Virol. 68, 7534-7536. 

Xi,Y.G., Ingrosso, L., Ladogana, A., Masullo, C., and Rocchiari, M. (1992). Amphotericin B treatment dissociates in vivo replication of the scrapie agent from RrR accumulation [see comments]. Nature356, 598-601. 

Garp, R.I., Ye, X., and Rubenstein, R. (1994). The nature of he scrapie agent. Biological characteristics of scrapie in different scrapie strain-host combinations. Ann. N.Y. Acad. Sd. 724, 221-234. 

Dickenson, A.G., Meikle, V., and Fraser, H. (1968) Identification of a gene which controls the incubation period of some strains of scrapie agent in mice./. Comp. Pathol. 78, 293-299. 

Race, E.R., Priola, S.A., Bessen, R.A., Ernst, D., Dockter, J., Mucke, L., Chesebro, B., and Oldstone, M.B.A. (1995). Neuron-specific expression of a hamster prion protein minigene in transgenic mice induces susceptibility to hamster scrapie agent. Neuron 15,1183-1191. 

That PrP is necessary for scrapie (Bueler et al, 1993) shows that PrP is important, but is not evidence that it is itself the scrapie agent. The control of the infection specificity by the PrP sequence (Prusiner et al, 1990) again shows PrP to be central to the disease process. 

Carp, R.I., Callahan, S.M., Sersen, E.A., and Moretz, R.C. 1984. Preclinical changes in weight of scrapie-infected mice as a function of scrapie agent-mouse strain combination. Intervirology 21, 61-69. 

Markovits, P., Dormont, D., Delpech, B., Court, L., and Latarjet, R. 1981. Trials of in vitro propagation of the scrapie agent in mouse nerve cells. C. R. Seances Acad. Sci. Ill 293, 413-417. 

Aguzzi, A. 2005. Prion toxicity aU sail and no anchor. Science 308 1420-1421 Alper, T., Haig, D. A., and Clarke, M. C. 1966. The exceptionally small size of the scrapie agent. Biochem. Biophys. Res. Commun. 22 278-284... 

E. Baldauf, M. Beekes and H. Diringer, Evidence for an alternative direct route of access for the scrapie agent to the brain bypassing the spinal cord,... 

S. Booth, C. Bowman, R. Baumgartner, G. Sorensen, C. Robertson, M. Coulthart, C. Phillipson and R. L. Somorjai, Identification of central nervous system genes involved in the host response to the scrapie agent during preclinical and clinical infection, J. Gen. Virol, 2004, 85(Pt 11), 3459-71. 

Gibbons RA, Hunter GD. Nature of the scrapie agent. Nature. 1967 215(5105) 1041-1043. 

Prusiner SB, Hadlow WJ, Eklund CM, Race RE. Sedimentation properties of the scrapie agent. Proc Natl Acad Sci... 

Prusiner SB, McKinley MP, Groth DF, et al. Scrapie agent contains a hydrophobic protein. Proc Natl Acad Sci USA. 1981 78(ll) 6675-6679. 

In mice affected with scrapie agent, there is a progressive increase in the activities of /3-glueuronidase and deoxyribonuclease in the brain, reaching a final level two to three times above the normal figure in affected animals (MilLson, 1965),... 

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