Deciphering Prion Diseases with Transgenic Mice

  • Glenn C. Telling
  • Michael Scott
  • Stanley B. Prusiner
Chapter
Part of the Serono Symposia USA Norwell, Massachusetts book series (SERONOSYMP)

Abstract

Prions cause a group of human and animal neurodegenerative diseases that are now classified together because their etiology and pathogenesis involve modification of the prion protein (PrP) (1). Prion diseases are manifest as infectious, genetic, and sporadic disorders (Table 16.1). These diseases can be transmitted among mammals by the infectious particle designated “prion” (2). Despite intensive searches over the past three decades, no nucleic acid has been found within prions (3–6), yet a modified isoform of the host-encoded PrP designated PrPSc is essential for infectivity (1, 7–10). In fact, considerable experimental data argue that prions are composed exclusively of PrPSc. Earlier terms used to describe the prion diseases include transmissible encephalopathies, spongiform encephalopathies, and slow virus diseases (11–13).

Keywords

Prion Protein Prion Disease Bovine Spongiform Encephalopathy Syrian Hamster Fatal Familial Insomnia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. 1.
    Prusiner SB. Molecular biology of prion diseases. Science 1991;252:1515–1522.PubMedCrossRefGoogle Scholar
  2. 2.
    Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science 1982;216:136–144.PubMedCrossRefGoogle Scholar
  3. 3.
    Alper T, Haig DA, Clarke MC. The exceptionally small size of the scrapie agent. Biochem Biophys Res Commun 1966;22:278–284.PubMedCrossRefGoogle Scholar
  4. 4.
    Alper T, Cramp WA, Haig DA, Clarke MC. Does the agent of scrapie replicate without nucleic acid? Nature 1967;214:764–766.PubMedCrossRefGoogle Scholar
  5. 5.
    Hunter GD. Scrapie: a prototype slow infection. J Infect Dis 1972;125:427–440.PubMedCrossRefGoogle Scholar
  6. 6.
    Riesner D, Kellings K, Meyer N, Mirenda C, Prusiner SB. Nucleic acids and scrapie prions. In: Prusiner SB, Collinge J, Powell J, et al., eds. Prion diseases of humans and animals. London: Ellis Horwood, 1992:341–358.Google Scholar
  7. 7.
    Prusiner SB, McKinley MP, Bowman KA, et al. Scrapie prions aggregate to form amyloid-like birefringent rods. Cell 1983;35:349–358.PubMedCrossRefGoogle Scholar
  8. 8.
    Büeler H, Aguzzi A, Sailer A, et al. Mice devoid of PrP are resistant to scrapie. Cell 1993;73:1339–1347.PubMedCrossRefGoogle Scholar
  9. 9.
    Prusiner SB, Groth D, Serban A, et al. Ablation of the prion protein (PrP) gene in mice prevents scrapie and facilitates production of anti-PrP antibodies. Proc Natl Acad Sci USA 1993;90:10608–10612.PubMedCrossRefGoogle Scholar
  10. 10.
    Prusiner SB, Groth D, Serban A, Stahl N, Gabizon R. Attempts to restore scrapie prion infectivity after exposure to protein denaturants. Proc Natl Acad Sci USA 1993;90:2793–2797.PubMedCrossRefGoogle Scholar
  11. 11.
    Sigurdsson B. Rida, a chronic encephalitis of sheep with general remarks on infections which develop slowly and some of their special characteristics. Br Vet J 1954;110:341–354.Google Scholar
  12. 12.
    Gajdusek DC. Unconventional viruses and the origin and disappearance of kuru. Science 1977;197:943–960.PubMedCrossRefGoogle Scholar
  13. 13.
    Gajdusek DC. Subacute spongiform virus encephalopathies caused by unconventional viruses. In: Maramorosch K, McKelvey JJ Jr, eds. Subviral pathogens of plants and animals: viroids and prions. Orlando: Academic Press, 1985:483–544.Google Scholar
  14. 14.
    Gajdusek DC, Gibbs CJ Jr, Alpers M. Experimental transmission of a kuru-like syndrome to chimpanzees. Nature 1966;209:794–796.PubMedCrossRefGoogle Scholar
  15. 15.
    Kirschbaum WR. Zwei eigenartige Erkrankungen des Zentralnervensystems nach Art der spastischen Pseudosklerose (Jakob). Z Ges Neurol Psychiatr 1924;92:175–220.CrossRefGoogle Scholar
  16. 16.
    Meggendorfer F. Klinische und genealogische Beobachtungen bei einem Fall von spastischer Pseudosklerose Jakobs. Z Ges Neurol Psychiatr 1930;128: 337–341.CrossRefGoogle Scholar
  17. 17.
    Sparkes RS, Simon M, Cohn VH, et al. Assignment of the human and mouse prion protein genes to homologous chromosomes. Proc Natl Acad Sci USA 1986;83:7358–7362.PubMedCrossRefGoogle Scholar
  18. 18.
    Hsiao K, Baker HF, Crow TJ, et al. Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome. Nature 1989;338:342–345.PubMedCrossRefGoogle Scholar
  19. 19.
    Prusiner SB. Inherited prion diseases. Proc Natl Acad Sci USA 1994;91: 4611–4614.PubMedCrossRefGoogle Scholar
  20. 20.
    Masters CL, Gajdusek DC, Gibbs CJ Jr. Creutzfeldt-Jakob disease virus isolations from the Gerstmann-Sträussler syndrome. Brain 1981;104:559–588.PubMedCrossRefGoogle Scholar
  21. 21.
    Prusiner SB. Scrapie prions. Annu Rev Microbiol 1989;43:345–374.PubMedCrossRefGoogle Scholar
  22. 22.
    Tateishi J, Doh-ura K, Kitamoto T, et al. Prion protein gene analysis and transmission studies of Creutzfeldt-Jakob disease. In: Prusiner SB, Collinge J, Powell J, et al., eds. Prion diseases of humans and animals. London: Ellis Horwood, 1992:129–134.Google Scholar
  23. 23.
    Malmgren R, Kurland L, Mokri B, Kurtzke J. The epidemiology of Creutzfeldt-Jakob disease. In: Prusiner SB, Hadlow WJ, eds. Slow transmissible diseases of the nervous system, vol 1. New York: Academic Press, 1979:93–112.Google Scholar
  24. 24.
    Brown P, Cathala F, Raubertas RF, Gajdusek DC, Castaigne P. The epidemiology of Creutzfeldt-Jakob disease: conclusion of 15-year investigation in France and review of the world literature. Neurology 1987;37:895–904.PubMedGoogle Scholar
  25. 25.
    Harries-Jones R, Knight R, Will RG, Cousens S, Smith PG, Matthews WB. Creutzfeldt-Jakob disease in England and Wales, 1980–1984: a case-control study of potential risk factors. J Neurol Neurosurg Psychiatry 1988;51: 1113–1119.PubMedCrossRefGoogle Scholar
  26. 26.
    Cousens SN, Harries-Jones R, Knight R, Will RG, Smith PG, Matthews WB. Geographical distribution of cases of Creutzfeldt-Jakob disease in England and Wales 1970–84. J Neurol Neurosurg Psychiatry 1990;53:459–465.PubMedCrossRefGoogle Scholar
  27. 27.
    Borchelt DR, Scott M, Taraboulos A, Stahl N, Prusiner SB. Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells. J Cell Biol 1990;110:743–752.PubMedCrossRefGoogle Scholar
  28. 28.
    Westaway D, DeArmond SJ, Cayetano-Canlas J, et al. Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice overexpressing wild-type prion proteins. Cell 1994;76:117–129.PubMedCrossRefGoogle Scholar
  29. 29.
    Masters CL, Harris JO, Gajdusek DC, Gibbs CJ Jr, Bernouilli C, Asher DM. Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann Neurol 1978;5:177–188.CrossRefGoogle Scholar
  30. 30.
    Gajdusek DC, Zigas V. Degenerative disease of the central nervous system in New Guinea—the endemic occurrence of “kuru” in the native population. N Engl J Med 1957;257:974–978.PubMedCrossRefGoogle Scholar
  31. 31.
    Gajdusek DC, Zigas V. Clinical, pathological and epidemiological study of an acute progressive degenerative disease of the central nervous system among natives of the eastern highlands of New Guinea. Am J Med 1959;26:442–469.PubMedCrossRefGoogle Scholar
  32. 32.
    Alpers M. Epidemiology and clinical aspects of kuru. In: Prusiner SB, McKinley MP, eds. Prions—novel infectious pathogens causing scrapie and Creutzfeldt-Jakob disease. Orlando: Academic Press, 1987:451–465.Google Scholar
  33. 33.
    Hsiao K, Prusiner SB. Inherited human prion diseases. Neurology 1990; 40:1820–1827.PubMedGoogle Scholar
  34. 34.
    Brown P. The phenotypic expression of different mutations in transmissible human spongiform encephalopathy. Rev Neurol 1992;148:317–327.PubMedGoogle Scholar
  35. 35.
    Medori R, Tritschler H-J, LeBlanc A, et al. Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene. N Engl J Med 1992;326:444–449.PubMedCrossRefGoogle Scholar
  36. 36.
    Hsiao KK, Scott M, Foster D, Groth DF, DeArmond SJ, Prusiner SB. Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science 1990;250:1587–1590.PubMedCrossRefGoogle Scholar
  37. 37.
    Hsiao KK, Groth D, Scott M, et al. Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein. Proc Natl Acad Sci USA 1994;91:9126–9130.PubMedCrossRefGoogle Scholar
  38. 38.
    Telling GC, Scott M, Hsiao KK, et al. Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein. Proc Natl Acad Sci USA 1994;91:9936–9940.PubMedCrossRefGoogle Scholar
  39. 39.
    Prusiner SB, Scott M, Foster D, et al. Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 1990;63:673–686.PubMedCrossRefGoogle Scholar
  40. 40.
    Scott M, Groth D, Foster D, et al. Propagation of prions with artificial properties in transgenic mice expressing chimeric PrP genes. Cell 1993;73:979–988.PubMedCrossRefGoogle Scholar
  41. 41.
    Stahl N, Borchelt DR, Hsiao K, Prusiner SB. Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell 1987;51:229–240.PubMedCrossRefGoogle Scholar
  42. 42.
    Gordon WS. Advances in veterinary research. Vet Res 1946;58:516–520.Google Scholar
  43. 43.
    Parry HB. In: Oppenheimer DR, ed. Scrapie disease in sheep. New York: Academic Press, 1983.Google Scholar
  44. 44.
    Parry HB. Scrapie: a transmissible and hereditary disease of sheep. Heredity 1962;17:75–105.PubMedCrossRefGoogle Scholar
  45. 45.
    Dickinson AG, Young GB, Stamp JT, Renwick CC. An analysis of natural scrapie in Suffolk sheep. Heredity 1965;20:485–503.PubMedCrossRefGoogle Scholar
  46. 46.
    Wilesmith JW, Ryan JBM, Hueston WD, Hoinville LJ. Bovine spongiform encephalopathy: epidemiological features 1985 to 1990. Vet Rec 1992;130:90–94.PubMedCrossRefGoogle Scholar
  47. 47.
    Stahl N, Baldwin MA, Teplow DB, et al. Structural analysis of the scrapie prion protein using mass spectrometry and amino acid sequencing. Biochemistry 1993;32:1991–2002.PubMedCrossRefGoogle Scholar
  48. 48.
    Pan K-M, Baldwin M, Nguyen J, et al. Conversion of α-helices into β-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci USA 1993;90:10962–10966.PubMedCrossRefGoogle Scholar
  49. 49.
    Pattison IH. Experiments with scrapie with special reference to the nature of the agent and the pathology of the disease. In: Gajdusek DC, Gibbs CJ Jr, Alpers MP, eds. Slow, latent and temperate virus infections, NINDB Monograph 2. Washington, DC: U.S. Government Printing, 1965:249–257.Google Scholar
  50. 50.
    Pattison IH. The relative susceptibility of sheep, goats and mice to two types of the goat scrapie agent. Res Vet Sci 1966;7:207–212.PubMedGoogle Scholar
  51. 51.
    Pattison IH, Jones KM. The possible nature of the transmissible agent of scrapie. Vet Rec 1967;80:1–8.CrossRefGoogle Scholar
  52. 52.
    Bockman JM, Prusiner SB, Tateishi J, Kingsbury DT. Immunoblotting of Creutzfeldt-Jakob disease prion proteins: host species-specific epitopes. Ann Neurol 1987;21:589–595.PubMedCrossRefGoogle Scholar
  53. 53.
    Wilesmith JW, Hoinville LJ, Ryan JBM, Sayers AR. Bovine spongiform encephalopathy: aspects of the clinical picture and analyses of possible changes 1986–1990. Vet Rec 1992;130:197–201.PubMedCrossRefGoogle Scholar
  54. 54.
    Goldmann W, Hunter N, Martin T, Dawson M, Hope J. Different forms of the bovine PrP gene have five or six copies of a short, G-C-rich element within the protein-coding exon. J Gen Virol 1991;72:201–204.PubMedCrossRefGoogle Scholar
  55. 55.
    Hope J, Reekie LJD, Hunter N, et al. Fibrils from brains of cows with new cattle disease contain scrapie-associated protein. Nature 1988;336:390–392.PubMedCrossRefGoogle Scholar
  56. 56.
    Prusiner SB, Fuzi M, Scott M, et al. Immunologic and molecular biological studies of prion proteins in bovine spongiform encephalopathy. J Infect Dis 1993;167:602–613.PubMedCrossRefGoogle Scholar
  57. 57.
    Scott M, Foster D, Mirenda C, et al. Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques. Cell 1989;59:847–857.PubMedCrossRefGoogle Scholar
  58. 58.
    Westaway D, Cooper C, Turner S, Da Costa M, Carlson GA, Prusiner SB. Structure and polymorphism of the mouse prion protein gene. Proc Natl Acad Sci USA 1994;91:6418–6422.PubMedCrossRefGoogle Scholar
  59. 59.
    Büeler H, Fischer M, Lang Y, et al. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 1992:356:577–582.PubMedCrossRefGoogle Scholar
  60. 60.
    Barry RA, Prusiner SB. Monoclonal antibodies to the cellular and scrapie prion proteins. J Infect Dis 1986;154:518–521.PubMedCrossRefGoogle Scholar
  61. 61.
    Kascsak RJ, Rubenstein R, Merz PA, et al. Mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins. J Virol 1987;61:3688–3693.PubMedGoogle Scholar
  62. 62.
    Rogers M, Serban D, Gyuris T, Scott M, Torchia T, Prusiner SB. Epitope mapping of the Syrian hamster prion protein utilizing chimeric and mutant genes in a vaccinia virus expression system. J Immunol 1991;147:3568–3574.PubMedGoogle Scholar
  63. 63.
    Brown P, Goldfarb LG, Kovanen J, et al. Phenotypic characteristics of familial Creutzfeldt-Jakob disease associated with the codon 178Asn PRNP mutation. Ann Neurol 1992;31:282–285.PubMedCrossRefGoogle Scholar
  64. 64.
    Medori R, Montagna P, Tritschler HJ, et al. Fatal familial insomnia: a second kindred with mutation of prion protein gene at codon 178. Neurology 1992;42:669–670.PubMedGoogle Scholar
  65. 65.
    Telling GT, Haga T, Torchia M, Tremblay P, DeArmond SJ, Prusiner SB. Interactions between wild-type and mutant prior proteins modulate neurodegeneration in transgenic mice. Genes Dev 1996 (in press).Google Scholar
  66. 66.
    Carlson GA, Ebeling C, Yang S-L, et al. Prion isolate specified allotypic interactions between the cellular and scrapie prion proteins in congenic and transgenic mice. Proc Natl Acad Sci USA 1994;91:5690–5694.PubMedCrossRefGoogle Scholar
  67. 67.
    Scott MR, Köhler R, Foster D, Prusiner SB. Chimeric prion protein expression in cultured cells and transgenic mice. Protein Sci 1992;1:986–997.PubMedCrossRefGoogle Scholar
  68. 68.
    Kretzschmar HA, Stowring LE, Westaway D, Stubblebine WH, Prusiner SB, DeArmond SJ. Molecular cloning of a human prion protein cDNA. DNA 1986;5:315–324.PubMedCrossRefGoogle Scholar
  69. 69.
    Raeber AJ, Borchelt DR, Scott M, Prusiner SB. Attempts to convert the cellular prion protein into the scrapie isoform in cell-free systems. J Virol 1992;66:6155–6163.PubMedGoogle Scholar
  70. 70.
    Oesch B, Teplow DB, Stahl N, Serban D, Hood LE, Prusiner SB. Identification of cellular proteins binding to the scrapie prion protein. Biochemistry 1990;29:5848–5855.PubMedCrossRefGoogle Scholar
  71. 71.
    Carlson GA, Ebeling C, Torchia M, Westaway D, Prusiner SB. Delimiting the location of the scrapie prion incubation time gene on chromosome 2 of the mouse. Genetics 1993;133:979–988.PubMedGoogle Scholar
  72. 72.
    Bruce ME, Dickinson AG, Fraser H. Cerebral amyloidosis in scrapie in the mouse: effect of agent strain and mouse genotype. Neuropathol Appl Neurobiol 1976;2:471–478.CrossRefGoogle Scholar
  73. 73.
    Cuillé J, Chelle PL. Experimental transmission of trembling to the goat. CR Seances Acad Sci 1939;208:1058–1060.Google Scholar
  74. 74.
    Dickinson AG, Stamp JT. Experimental scrapie in Cheviot and Suffolk sheep. J Comp Pathol 1969;79:23–26.PubMedCrossRefGoogle Scholar
  75. 75.
    Hadlow WJ, Kennedy RC, Race RE. Natural infection of Suffolk sheep with scrapie virus. J Infect Dis 1982;146:657–664.PubMedCrossRefGoogle Scholar
  76. 76.
    Hadlow WJ, Kennedy RC, Race RE, Eklund CM. Virologic and neurohistologic findings in dairy goats affected with natural scrapie. Vet Pathol 1980;17:187–199.PubMedCrossRefGoogle Scholar
  77. 77.
    Gordon WS. Variation in susceptibility of sheep to scrapie and genetic implications. In: Report of scrapie seminar, ARS 91-53. Washington, DC: U.S. Department of Agriculture, 1966:53–67.Google Scholar
  78. 78.
    Pattison IH, Millson GC. Scrapie produced experimentally in goats with special reference to the clinical syndrome. J Comp Pathol 1961;71:101–108.PubMedGoogle Scholar
  79. 79.
    Dickinson AG, Fraser H. An assessment of the genetics of scrapie in sheep and mice. In: Prusiner SB, Hadlow WJ, eds. Slow transmissible diseases of the nervous system, vol 1. New York: Academic Press, 1979:367–386.Google Scholar
  80. 80.
    Bruce ME, Dickinson AG. Biological evidence that the scrapie agent has an independent genome. J Gen Virol 1987;68:79–89.PubMedCrossRefGoogle Scholar
  81. 81.
    Kimberlin RH, Cole S, Walker CA. Temporary and permanent modifications to a single strain of mouse scrapie on transmission to rats and hamsters. J Gen Virol 1987;68:1875–1881.PubMedCrossRefGoogle Scholar
  82. 82.
    Dickinson AG, Outram GW. Genetic aspects of unconventional virus infections: the basis of the virino hypothesis. In: Bock G, Marsh J, eds. Novel infectious agents and the central nervous system. Ciba Foundation Symposium 135. Chichester, UK: John Wiley and Sons, 1988:63–83.Google Scholar
  83. 83.
    Dickinson AG, Meikle VMH, Fraser H. Identification of a gene which controls the incubation period of some strains of scrapie agent in mice. J Comp Pathol 1968;78:293–299.PubMedCrossRefGoogle Scholar
  84. 84.
    Fraser H, Dickinson AG. Scrapie in mice. Agent-strain differences in the distribution and intensity of grey matter vacuolation. J Comp Pathol 1973;83:29–40.PubMedCrossRefGoogle Scholar
  85. 85.
    Bruce ME, McBride PA, Farquhar CF. Precise targeting of the pathology of the sialoglycoprotein, PrP, and vacuolar degeneration in mouse scrapie. Neurosci Lett 1989;102:1–6.PubMedCrossRefGoogle Scholar
  86. 86.
    Hecker R, Taraboulos A, Scott M, et al Replication of distinct prion isolates is region specific in brains of transgenic mice and hamsters. Genes Dev 1992;6:1213–1228.PubMedCrossRefGoogle Scholar
  87. 87.
    Dickinson AG, Meikle VMH. Host-genotype and agent effects in scrapie incubation: change in allelic interaction with different strains of agent. Mol Gen Genet 1971;112:73–79.PubMedCrossRefGoogle Scholar
  88. 88.
    Dickinson AG, Bruce ME, Outram GW, Kimberlin RH. Scrapie strain differences: the implications of stability and mutation. In: Tateishi J, ed. Proceedings of workshop on slow transmissible diseases. Tokyo: Japanese Ministry of Health and Welfare, 1984:105–118.Google Scholar
  89. 89.
    Kingsbury DT, Kasper KC, Stites DP, Watson JD, Hogan RN, Prusiner SB. Genetic control of scrapie and Creutzfeldt-Jakob disease in mice. J Immunol 1983;131:491–496.PubMedGoogle Scholar
  90. 90.
    Carp RI, Moretz RC, Natelli M, Dickinson AG. Genetic control of scrapie: incubation period and plaque formation in mice. J Gen Virol 1987;68:401–407.PubMedCrossRefGoogle Scholar
  91. 91.
    Carlson GA, Kingsbury DT, Goodman PA, et al. Linkage of prion protein and scrapie incubation time genes. Cell 1986;46:503–511.PubMedCrossRefGoogle Scholar
  92. 92.
    Hunter N, Hope J, McConnell I, Dickinson AG. Linkage of the scrapie-associated fibril protein (PrP) gene and Sinc using congenic mice and restriction fragment length polymorphism analysis. J Gen Virol 1987;68:2711–2716.PubMedCrossRefGoogle Scholar
  93. 93.
    Race RE, Graham K, Ernst D, Caughey B, Chesebro B. Analysis of linkage between scrapie incubation period and the prion protein gene in mice. J Gen Virol 1990;71:493–497.PubMedCrossRefGoogle Scholar
  94. 94.
    Ziegler DR. In: O’Brien SJ, ed. Genetic maps—locus maps of complex genomes. 6th ed. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1993;4.42–4.45.Google Scholar
  95. 95.
    Westaway D, Goodman PA, Mirenda CA, McKinley MP, Carlson GA, Prusiner SB. Distinct prion proteins in short and long scrapie incubation period mice. Cell 1987;51:651–662.PubMedCrossRefGoogle Scholar
  96. 96.
    Westaway D, Mirenda CA, Foster D, et al. Paradoxical shortening of scrapie incubation times by expression of prion protein transgenes derived from long incubation period mice. Neuron 1991;7:59–68.PubMedCrossRefGoogle Scholar
  97. 97.
    Carlson GA, Westaway D, DeArmond SJ, Peterson-Torchia M, Prusiner SB. Primary structure of prion protein may modify scrapie isolate properties. Proc Natl Acad Sci USA 1989;86:7475–7479.PubMedCrossRefGoogle Scholar
  98. 98.
    Dickinson AG, Meikle VM. A comparison of some biological characteristics of the mouse-passaged scrapie agents, 22A and ME7. Genet Res 1969;13:213–225.PubMedCrossRefGoogle Scholar
  99. 99.
    Dickinson AG, Outram GW. The scrapie replication-site hypothesis and its implications for pathogenesis. In: Prusiner SB, Hadlow WJ, eds. Slow transmissible diseases of the nervous system, vol 2. New York: Academic Press, 1979:13–31.Google Scholar
  100. 100.
    Palmer MS, Dryden AJ, Hughes JT, Collinge J. Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease. Nature 1991; 352:340–342.PubMedCrossRefGoogle Scholar
  101. 101.
    Fraser H. Neuropathology of scrapie: the precision of the lesions and their diversity. In: Prusiner SB, Hadlow WJ, eds. Slow transmissible diseases of the nervous system, vol 1. New York: Academic Press, 1979:387–406.Google Scholar
  102. 102.
    Taraboulos A, Jendroska K, Serban D, Yang S-L, DeArmond SJ, Prusiner SB. Regional mapping of prion proteins in brains. Proc Natl Acad Sci USA 1992;89:7620–7624.PubMedCrossRefGoogle Scholar
  103. 103.
    DeArmond SJ, Yang S-L, Lee A, et al. Three scrapie prion isolates exhibit different accumulation patterns of the prion protein scrapie isoform. Proc Natl Acad Sci USA 1993;90:6449–6453.PubMedCrossRefGoogle Scholar
  104. 104.
    DeArmond SJ, Mobley WC, DeMott DL, Barry RA, Beckstead JH, Prusiner SB. Changes in the localization of brain prion proteins during scrapie infection. Neurology 1987;37:1271–1280.PubMedGoogle Scholar
  105. 105.
    Casaccia-Bonnefil P, Kascsak RJ, Fersko R, Callahan S, Carp RI. Brain regional distribution of prion protein PrP27-30 in mice stereotaxically microinjected with different strains of scrapie. J Infect Dis 1993;167:7–12.PubMedCrossRefGoogle Scholar
  106. 106.
    Bruce ME, McConnell I, Fraser H, Dickinson AG. The disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis. J Gen Virol 1991;72: 595–603.PubMedCrossRefGoogle Scholar
  107. 107.
    Marsh RF, Bessen RA, Lehmann S, Hartsough GR. Epidemiological and experimental studies on a new incident of transmissible mink encephalopathy. J Gen Virol 1991;72:589–594.PubMedCrossRefGoogle Scholar
  108. 108.
    Bessen RA, Marsh RF. Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent. J Virol 1992;66:2096–2101.PubMedGoogle Scholar
  109. 109.
    Bessen RA, Marsh RF. Identification of two biologically distinct strains of transmissible mink encephalopathy in hamsters. J Gen Virol 1992;73:329–334.PubMedCrossRefGoogle Scholar
  110. 110.
    Bellinger-Kawahara CG, Kempner E, Groth DF, Gabizon R, Prusiner SB. Scrapie prion liposomes and rods exhibit target sizes of 55,000 Da. Virology 1988;164:537–541.PubMedCrossRefGoogle Scholar
  111. 111.
    Lacroute F. Non-mendelian mutation allowing ureidosuccinic acid uptake in yeast. J Bacteriol 1971;106:519–522.PubMedGoogle Scholar
  112. 112.
    Wickner RB. [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science 1994;264:566–569.PubMedCrossRefGoogle Scholar
  113. 113.
    Coschigano PW, Magasanik B. The URE2 gene product of Saccharomyces cerevisiae plays an important role in the cellular response to the nitrogen source and has homology to glutathione S-transferases. Mol Cell Biol 1991;11:822–832.PubMedGoogle Scholar
  114. 114.
    Cox BS, Tuite MF, McLaughlin CS. The psi factor of yeast: a problem in inheritance. Yeast 1988;4:159–178.PubMedCrossRefGoogle Scholar
  115. 115.
    Deleu C, Clavé C, Bégueret J. A single amino acid difference is sufficient to elicit vegetative incompatibility in the fungus Podospora anserina. Genetics 1993;135:45–52.PubMedGoogle Scholar
  116. 116.
    Schellenberg GD, Bird TD, Wijsman EM, et al. Genetic linkage evidence for a familial Alzheimer’s disease locus on chromosome 14. Science 1992;258: 668–671.PubMedCrossRefGoogle Scholar
  117. 117.
    Van Broeckhoven C, Backhovens H, Cruts M, et al. Mapping of a gene predisposing to early-onset Alzheimer’s disease to chromosome 14q24.3. Nat Genet 1992;2:335–339.PubMedCrossRefGoogle Scholar
  118. 118.
    Van Broeckhoven C, Haan J, Bakker E, et al. Amyloid β protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch). Science 1990;248:1120–1122.PubMedCrossRefGoogle Scholar
  119. 119.
    Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral slerosis. Nature 1993;362:59–62.PubMedCrossRefGoogle Scholar
  120. 120.
    Mullan M, Houlden H, Windelspecht M, et al. A locus for familial early-onset Alzheimer’s disease on the long arm of chromosome 14, proximal to the α1-antichymotrypsin gene. Nat Genet 1992;2:340–342.PubMedCrossRefGoogle Scholar
  121. 121.
    Goate A, Chartier-Harlin M-C, Mullan M, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 1991;349:704–706.PubMedCrossRefGoogle Scholar
  122. 122.
    St. George-Hyslop P, Haines J, Rogaev E, et al. Genetic evidence for a novel familial Alzheimer’s disease locus on chromosome 14. Nat Genet 1992;2: 330–334.PubMedCrossRefGoogle Scholar
  123. 123.
    Levy E, Carman MD, Fernandez-Madrid IJ, et al. Mutation of the Alzheimer’s disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science 1990;248:1124–1126.PubMedCrossRefGoogle Scholar
  124. 124.
    Rogers M, Yehiely F, Scott M, Prusiner SB. Conversion of truncated and elongated prion proteins into the scrapie isoform in cultured cells. Proc Natl Acad Sci USA 1993;90:3182–3186.PubMedCrossRefGoogle Scholar
  125. 125.
    Monari L, Chen SG, Brown P, et al. Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism. Proc Natl Acad Sci USA 1994;91:2839–2842.PubMedCrossRefGoogle Scholar
  126. 126.
    Prusiner SB, Hsiao KK. Human prion diseases. Ann Neurol 1994;35:385–395.PubMedCrossRefGoogle Scholar
  127. 127.
    Cohen FE, Pan K-M, Huang Z, Baldwin M, Fletterick RJ, Prusiner SB. Structural clues to prion replication. Science 1994;264:530–531.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1996

Authors and Affiliations

  • Glenn C. Telling
  • Michael Scott
  • Stanley B. Prusiner

There are no affiliations available

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