Springer Protocols: Abstract: The Mouse Model for Scrapie: Inoculation, Clinical Scoring, and Histopathological Techniques

The Mouse Model for Scrapie: Inoculation, Clinical Scoring, and Histopathological Techniques

By: Harry C. Meeker², Xuemin Ye², Richard I. Carp²

Abstract

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The mouse is a popular and versatile model for the study of scrapie and other transmissible spongiform encephalopathies. In this chapter, information is given for preparation of infect ious material for inoculation and a method of clinical scoring that yields accurate and repro duciblequantification of the scrapie incubation period. With the help of histopathological and immunopathological techniques, we can detect brain pathological changes in scrapie-infected animals at the cellular and molecular level. We will also describe the histological and immuno cytochemistry methods we use for scrapie research, outline step-by-step procedures, discuss tis sue preparation, fixation, and processing of specimens, and provide special hints to achieve successful staining. We also include our results of PrP^Sc and GFAP immunostaining in scrapie research. In conclusion, immunopathological staining is an important and useful tool in the research of scrapie pathology.

Affiliation(s): (2) Department of Virology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY

Book Title: Amyloid Proteins: Methods and Protocols

Series: Methods in Molecular Biology | Volume: 299 | Pub. Date: Dec-28-2004 | Page Range: 309-323 | DOI: 10.1385/1-59259-874-9:309

Subject: Protein Science

Key Words: Mouse - scrapie - inoculation - brain - istopathology - immunohistopathology - PrPSc - GFAP

References

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1.	Prusiner, S. B., Scott, M., Foster, D., et al. (1990) Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63, 673–686.

2.	Collinge, J., Palmer, M. S., Sidle, K. C. L., et al. (1995) Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature 378, 21–28.

3.	Vilotte, J. L., Soulier, S., Essalmani, R., et al. (2001) Markedly increased susceptibility to natural sheep scrapie of transgenic mice expressing ovine PrP. J. Virol. 75, 5977–5984.

4.	Chiesa, R., Piccardo, P., Ghetti, B., and Harris, D. A. (1998) Neurological illness in transgenic mice expressing a prion protein with an insertional mutation. Neuron 21, 1339–1351.

5.	Raeber, A. J., Brandnar, S., Klein, M. A., et al. (1998) Transgenic and knockout mice in research on prion diseases. Brain Pathol. 8, 715–733.

6.	Oldstone, M. B., Race, R., Thomas, D., et al. (2002) Lymphotoxin-α-and lymphotoxin-ß-deficient mice differ in susceptibility to scrapie: evidence against dendritic cell involvement in neuroinvasion. J. Virol. 76, 4357–4363.

7.	Prinz, M., Heikenwalder, M., Schwarz, P., Takeda, K., Akira, S., and Aguzzi, A. (2003) Prion pathogenesis in the absence of Toll-like receptor signaling. EMBO Reports 4, 195–199.

8.	Outram, G. W. (1976) The pathogenesis of scrapie in mice, in Slow Virus Diseases of Animals and Man (Kimberlin, R. H., ed.), Elsevier, North Holland, Amsterdam, pp. 325–358.

9.	Kimberlin, R. H. and Walker, C. A. (1979) Pathogenesis of mouse scrapie: dynamics of agent replication in spleen, spinal cord and brain after infection by different routes. J. Comp. Pathol. 89, 551–562.

10.	Bruce, M. E. and Fraser, H. (1981) Effect of route of injection on the frequency and distribution of cerebral amyloid plaques in scrapie mice. Neuropathol. Appl. Neurobiol. 7, 289–298.

11.	Fraser, H. (1979) Neuropathology of scrapie: the precision of the lesions and their diversity, in Slow Transmissible Diseases of the Central Nervous System, Vol. 1 (Prusiner, S. B. and Hadlow, W. J., eds.), Academic Press, NY, pp. 387–406.

12.	Fraser, H. and Bruce, M. E. (1973) Argyrophilic plaques in mice inoculated with scrapie from particular sources. Lancet I, 617–618.

13.	Wisniewski, H. M., Bruce, M. E., and Fraser, H. (1975) Infectious etiology of neuritic (senile) plaques in mice. Science 190, 1108–1110.

14.	Kim, Y. S., Carp, R. I., Callahan, S. M., Natelli, M., and Wisniewski, H. M. (1990) Vacuolization, incubation period and survival time in three mouse genotypes injected stereotactically in three brain regions with the 22L scrapie strain. J. Neuropathol. Exp. Neurol. 49, 106–113.

15.	Rubenstein, R., Merz, P. A., Kascsak, R. J., et al. (1991) Scrapie-infected spleens: analysis of infectivity, scrapie-associated fibrils and protease-resistant proteins. J. Infect. Dis. 164, 24–35.

16.	Eklund, C. M., Kennedy, R. C., and Hadlow, W. J. (1967) Pathogenesis of scrapie virus infection in the mouse. J. Infect. Dis. 117, 15–22.

17.	Carp, R. I., Kim, Y. S., and Callahan, S. M. (1989) Scrapie-induced alterations in glucose tolerance in mice. J. Gen. Virol. 70, 827–835.

18.	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. Intervirol. 21, 61–69.

19.	Dickinson, A. G. and Meikle, V. M. (1969) A comparison of some biological characteristics of the mouse-passaged scrapie agents, 22A and ME7. Genet. Res. 13, 213–225.

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

21.	Carlson, G. A., Kingsbury, D. T., Goodman, P. A., et al. (1986) Linkage of prion protein and scrapie incubation time genes. Cell 46, 503–511.

22.	Hunter, N. J., Hope, J., McConnell, I., and Dickinson, A. G. (1987) Linkage of the scrapie-associated fibril protein (PrP) gene and Sinc using congenic mice and restriction fragment length polymorphism analysis. J. Gen. Virol. 68, 2711–2716.

23.	Dickinson, A. G. and Fraser, H. (1979) The assessment of the genetics of scrapie in sheep and mice, in Slow Transmissible Diseases of the Central Nervous System, Vol. 1 (Prusiner, S. B. and Hadlow, W. J., eds.), Academic Press, NY, pp. 13–32.

24.	Carp, R. I., Moretz, R. C., Natelli, M., and Dickinson, A. G. (1987) Genetic control of scrapie: incubation period and plaque formation in I mice. J. Gen. Virol. 68, 401–407.

25.	Vaughn, J. E., Barber, R. P., Ribak, C. E., and Houser, C. R. (1981) Methods for the immunocytochemical localization of protein and peptide involved in neurotransmission, in Current Trends in Morphological Techniques (Johnson, J. E., ed.), CRC Press, Boca Raton, FL, pp. 33–70.

26.	Fraser, H. and Dickinson, A. G. (1970) Pathogenesis of scrapie in the mouse: the role of the spleen. Nature 226, 462–463.

27.	Clarke, M. C. and Haig, D. A. (1971) Multiplication of scrapie agent in mouse spleen. Res. Vet. Sci. 12, 195–197.

28.	Aucouturier, P., Geissman, F., Damotte, D., et al. (2002) Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie. J. Clin. Invest. 108, 703–708.

29.	Eklund, C. M., Hadlow, W. J., and Kennedy, R. C. (1963) Some properties of the scrapie agent and its behavior in mice. Proc. Soc. Exp. Biol. Med. 112, 974–979.

30.	Carp, R. I. (1982) Transmission of scrapie by the oral route: effect of gingival scarification. Lancet 1, 170–171.

31.	Thackray, A. M., Klein, M. A., and Bujdoso, R. (2003) Subclinical prion disease induced by oral inoculation. J. Virol. 77, 7991–7998.

32.	Glatzel, M. and Aguzzi, A. (2000) Peripheral pathogenesis of prion diseases. Microbes Infect. 2, 613–619.

33.	Baier, M., Norley, S., Schultz, J., Burminkel, M. K., Schwarz, A., and Reimer, C. (2003) Prion diseases: infectious and lethal doses following oral challenges. J. Gen. Virol. 84, 1927–1929.

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