Pathology and Pathogenesis of Bovine Spongiform Encephalopathy and Scrapie

  • M. Jeffrey
  • L. González
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 284)


In common with other prion diseases or transmissible spongiform encephalopathies (TSEs), scrapie of sheep and bovine spongiform encephalopathy (BSE) are characterized by grey matter vacuolation and accumulation of an abnormal isoform of the host prion protein (PrP) in the central nervous system (CNS). In apparent contrast with human disease, neither neuronal loss nor gliosis are invariable features of the pathology of domestic food animal TSEs. In sheep, accumulation of abnormal PrP may also occur in the lymphoreticular and peripheral nervous systems where it may be detected within months of birth. The involvement of tissues other than CNS is influenced by dose, PrP genotype of the host and strain of TSE agent. Although many different strains of scrapie agent have been isolated in rodents following serial passage of affected sheep brain tissue, the significance of these murine strains for natural sheep scrapie, and the extent to which different sheep scrapie strains occur naturally are uncertain. Whereas the consistent vacuolar pattern in the brains of BSE-affected cattle suggests a single strain of agent, the patterns of vacuolation in sheep scrapie are highly variable and cannot be easily used to define strain. In sheep scrapie, immunohistochemistry can be used to visualize different morphological types of abnormal PrP within individual brains. These different types of PrP accumulation seem to be associated with different brain cell types and with variation in the processing of abnormal PrP. When assessed in whole brain, different patterns of PrP accumulation are helpful in distinguishing between different sheep scrapie strains and also between ovine BSE and natural sheep scrapie.


Prion Protein Bovine Spongiform Encephalopathy Bovine Spongiform Encephalopathy Case Scrapie Strain Natural Scrapie 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aguzzi A, Weissmann C (1997) Prion Research—The Next Frontiers. Nature 389: 795–798PubMedCrossRefGoogle Scholar
  2. Andreoletti O, Berthon P, Marc D, Sarradin P, Grosclaude J, vanKeulen L, Schelcher F, Elsen JM and Lantier F (2000) Early accumulation of PrPs` in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie. J Gen.Virol 81: 3115–3126PubMedGoogle Scholar
  3. Austin AR, Pawson L, Meek S and Webster S (1997) Abnormalities of Heart Rate andGoogle Scholar
  4. Rhythm in Bovine Spongiform Encephalopathy. Vet Rec 141:352–357Google Scholar
  5. Austin AR, Simmons MM (1993) Reduced rumination in bovine spongiform encephalopathy and scrapie. Vet Rec 132: 324–325PubMedCrossRefGoogle Scholar
  6. Baron TGM, Madec JY, Calavas D, Richard Y, and Barillet F (2000) Comparison of French natural scrapie isolates with bovine spongiform encephalopathy and experimental scrapie infected sheep. Neurosci Lett 284: 175–178PubMedCrossRefGoogle Scholar
  7. Pathology and Pathogenesis of Bovine Spongiform Encephalopathy and Scrapie 91Google Scholar
  8. Beck E, Daniel PM, Parry HB (1964) Degeneration of the cerebellar and hypothalamic neurohypophysial systems in sheep with scrapie; and its relationship to human system degenerations. Brain 87: 153–176PubMedCrossRefGoogle Scholar
  9. Beekes M and McBride PA (2000) Early accumulation of pathological PrP in the enteric nervous system and gut-associated lymphoid tissue of hamsters orally infected with scrapie. Neurosci Lett 278: 181–184.PubMedCrossRefGoogle Scholar
  10. Begara-McGorum I, Gonzalez L, Simmons M, Hunter N, Houston F, and Jeffrey M (2002) Vacuolar lesion profile is sheep scrapie. Analysis of factors involved in its variation and relationship to disease specific accumulation. J Comp Pathol 127: 59–68Google Scholar
  11. Bessen RA and Marsh RF (1994) Distinct PrP Properties Suggest the Molecular Basis of Strain Variation in Transmissible Mink Encephalopathy. Virol 68: 7859–7868Google Scholar
  12. Birkett CR, Hennion RM, Bembridge DA, Clarke MC, Chree A, Bruce M E, and Bostock CJ (2001) Scrapie strains maintain biological phenotypes on propagation in a cell line in culture. EMBO J 20: 3351–3358PubMedCrossRefGoogle Scholar
  13. Bossers A, Belt PBGM, Raymond GJ, Caughey B, deVries R, Smits MA (1997) Scrapie susceptibility-linked polymorphisme modulate the in vitro conversion of sheep prion protein to protease-resistant forms. PNAS 94: 4931–4936PubMedCrossRefGoogle Scholar
  14. Brown KL, Stewart K, Bruce ME, Fraser H (1996) Scrapie in immunodeficient mice. In: Court L, Dodet B (eds) Transmissible Subacute Spongiform Encephalopathies: Prion Diseases. Elsevier Editions Scientifiques, Paris. pp 159–166Google Scholar
  15. Bruce ME and McBride PA (1990) Neuroanatomical distribution of PrP accumulation in mice infected with different strains of scrapie. Neuropath Appl Neurobiol 16: 541Google Scholar
  16. Bruce M, Chree A, McConnell I, Brown K and Fraser H (1996) Transmission and strain typing studies of scrapie and bovine spongiform encephalopathy. In: Court L, Dodet B (eds) Transmissible Subacute Spongiform Encephalopathies: Prion Diseases. Elsevier Editions Scientifiques, Paris. pp 259Google Scholar
  17. Bruce M, Chree A, McConnell I, Foster J, Pearson G and Fraser H (1994) Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and the species barrier. Phil Trans Roy Soc 343: 405–411CrossRefGoogle Scholar
  18. Bruce ME, Boyle A, Cousens S, McConnell I, Foster J, Goldmann W and Fraser H (2002) Strain characterization of natural sheep scrapie and comparison with BSE. J Gen Virol 83: 695–704PubMedGoogle Scholar
  19. Bruce ME, Fraser H, McBride PA, Scott JR and Dickinson AG (1992) The basis of strain variation in scrapie Prion diseases of humans and animals [edited by Prusiner SB, Collinge J, Powell J, Anderton B.[Ellis Horwood, LondonGoogle Scholar
  20. Bruce ME, McBride PA, Farquhar CF (1989) Precise Targeting of the Pathology of the Sialoglycoprotein, PrP, and Vacuolar Degeneration in Mouse Scrapie. Neurosci Lett 102: 1–6Google Scholar
  21. Chaplin MJ, Aldrich AD, Stack MJ (1998) Scrapie associated fibril detection from formaldehyde fixed brain tissue in natural cases of ovine scrapie. Res Vet Sci 64: 41–44PubMedCrossRefGoogle Scholar
  22. Collinge J, Sidle KCL, Meads J, Ironside J and Hill AF (1996) Molecular analysis of prion strain variation and the aetiology of `new variant’ CJD. Nature 383: 685–690PubMedCrossRefGoogle Scholar
  23. Cunningham A, Wells G, Scott A, Kirkwood J and Barnett J (1993) Transmissible spongiform encephalopathy in greater kudu (Tragelaphus strepsiceros) Vet Rec 132: 68PubMedGoogle Scholar
  24. Cutlip RC, Miller JM, Hamir AN, Peters J, Robinson MM, Jenny AL, Lehmkuhl HD, Taylor WD and Bisplinghoff FD (2001) Resistance of cattle to scrapie by the oral route. Can J Vet Res 65: 131–132PubMedGoogle Scholar
  25. Cutlip RC, Miller JM, Lehmkuhl HD (1997) Second passage of a US scrapie agent in cattle. J Comp Pathol 117: 271–275PubMedCrossRefGoogle Scholar
  26. DeArmond SJ, Kristensson K, Bowler RP (1992) PrPsc Causes Nerve Cell Death and Stimulates Astrocyte Proliferation: A Paradox. Prog Brain Res 94: 437–446Google Scholar
  27. DeArmond SJ (1998) Prion Diseases—The Spectrum of Etiologic and Pathogenic Mechanisms. In: Folstein MF (ed) Neurobiology of Primary Dementia. American Psychiatric Press, Inc, 1400 K St NW/Washington/DC 20005, pp 83–118Google Scholar
  28. DeArmond SJ, Qiu Y, Sanchez H, Spilman PR, NinchakCasey A, Alonso D and Daggett V (1999) PrPC glycoform heterogeneity as a function of brain region: Implications for selective targeting of neurons by prion strains. J Neuropath Exp Neurol 58: 1000–1009Google Scholar
  29. DeArmond SJ, Sanchez H, Yehiely F, Qiu Y, NinchakCasey A, Daggett V, Camerino AP, Cayetano J, Rogers M, Groth D, Torchia M, Tremblay P, Scott MR, Cohen FE and Prusiner SB (1997) Selective neuronal targeting in prion disease. Neuron 19: 1337–1348PubMedCrossRefGoogle Scholar
  30. Ersdal C, Simmons MM, Goodsir C, Martin S and Jeffrey M (2003) Sub-cellular pathology of scrapie: coated pits are increased in PrP codon 136 alanine homozygous scrapie-affected sheep. Acta Neuropathol 106: 17–28PubMedGoogle Scholar
  31. Fankhauser R, Fatzer R, Frauchiger E (1972) Spastic paralysis in cattle. Schweiz Arch Tierheilkd 114: 24–32PubMedGoogle Scholar
  32. Farquhar CF, Somerville RA, Ritchie LA (1989) Post-mortem immunodiagnosis of scrapie and bovine spongiform encephalopathy. J Virol Met 24: 215–222CrossRefGoogle Scholar
  33. Farquhar CF, Somerville RA, Bruce ME (1998) Straining the prion hypothesis. Nature 391: 345–346PubMedCrossRefGoogle Scholar
  34. Fraser H (1976) The pathology of natural and experimental scrapie. In: Kimberlin RH (ed) Slow virus diseases of animals and man. North-Holland Publishing Company, Amsterdam, pp 267–305Google Scholar
  35. Fraser H, Brown KL, Stewart K, McConnell I, McBride P, and Williams A (1996) Replication of scrapie in spleens of SCID mice follows reconstitution with wild-type mouse bone marrow. J Gen Virol 77: 1935–1940PubMedCrossRefGoogle Scholar
  36. Gibson PH, Somerville RA, Fraser H, Foster JD, and Kimberlin RH (1987) Scrapie associated fibrils in the diagnosis of scrapie in sheep. Vet Rec 120: 125–127PubMedCrossRefGoogle Scholar
  37. Goldmann W, Hunter N, Martin T, Dawson M and Hope J (1991) 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 72: 201–204Google Scholar
  38. Gonzalez L, Martin S, Begara-McGorum I, Hunter N, Houston F, Simmons M, and Jeffrey M (2002) Effects of agent strain and host genotype on PrP accumulation in the brain of sheep naturally and experimentally affected with scrapie. J Comp Pathol 126: 17–29PubMedCrossRefGoogle Scholar
  39. Pathology and Pathogenesis of Bovine Spongiform Encephalopathy and Scrapie 93Google Scholar
  40. Gonzalez L, Martin S, Jeffrey M (2003) Distinct profiles of PrPd immunoreactivity in the brain of scrapie and BSE infected sheep: implications on differential cell targeting and PrP processing. J Gen Virol 84: 1339–1350PubMedCrossRefGoogle Scholar
  41. Groschup M H, Beekes M, McBride PA, Hardt M, Hainfellner J A and Budka H. (1999) Deposition of disease-associated prion protein involves the peripheral nervous system in experimental scrapie. Acta Neuropathol. 98: 453–457PubMedCrossRefGoogle Scholar
  42. Hadlow WJ, Kennedy RC, Race RE (1982) Natural infection of Suffolk sheep with scrapie virus. Journal of Infectious diseases 146: 657–664PubMedCrossRefGoogle Scholar
  43. Hardt M, Baron T, Groschup, MH (2000) A comparative study of immunohistochemical methods for detecting abnormal prion protein with monoclonal and polyclonal antibodies. J Comp Pathol 122: 43–53PubMedCrossRefGoogle Scholar
  44. Haritani M, Spencer YI, Wells GAH (1994) Hydrated autoclave pretreatment enhancement of prion protein immunoreactivity in formalin fixed bovine spongiform encephalopathy affected brain. Acta Neuropathol 87: 86–90PubMedCrossRefGoogle Scholar
  45. Harris DA (1997) Cell biological studies of the prion protein. In: Harris DA (ed) Prions: Molecular and Cellular Biology. Horizon Scientific Press, Wymondham, UK, pp 53–65Google Scholar
  46. Heggebi3 R, Gonzalez L, Press CM, Gunnes G, Espenes A, Jeffrey M (2003) Disease-associated PrP in the enteric nervous system of scrapie-affected Suffolk sheep. J Gen Virol 84: 1327–1338CrossRefGoogle Scholar
  47. Heggebr R, Press CM, Gunnes G, Gonzalez L and Jeffrey M (2002) Distribution and accumulation of PrP in gut-associated and peripheral lymphoid tissue of scrapieaffected Suffolk sheep. J Gen Virol 83: 479–489Google Scholar
  48. Heggeba R, Press CM, Gunnes G, Lie KI, Tranulis MA, Ulvund M, Groschup MH, and Landsverk T (2000) Distribution of prion protein in the ileal Peyer’s patch of scrapie-free lambs and lambs naturally and experimentally exposed to the scrapie agent. J Gen Virol 81: 2327–2337Google Scholar
  49. Hope J, Wood SCER, Birkett CR, Chong A, Bruce ME, Cairns D, Goldmann W, Hunter N and Bostock CJ (1999) Molecular analysis of ovine prion protein identifies similarities between BSE and an experimental isolate of natural scrapie, CH1641. J Gen Virol 80: 1–4PubMedGoogle Scholar
  50. Houston EF, Halliday SI, Jeffrey M, Goldmann W and Hunter N (2002) New Zealand sheep with scrapie-susceptible PrP genotypes succumb to experimental challenge with a sheep-passaged scrapie isolate (SSBP/1) J Gen Virol 83: 1247–1250PubMedGoogle Scholar
  51. Hunter N (1997) PrP genetics in sheep and the implications for scrapie and BSE. TIMS 5: 331–334Google Scholar
  52. Hunter N (1998) Scrapie. Mol Biotech 9: 225–234CrossRefGoogle Scholar
  53. Hunter N, Goldmann W, Smith G and Hope J (1994) Frequencies of PRP Gene Variants in Healthy Cattle and Cattle with BSE in Scotland. Vet Rec 135: 400–403PubMedCrossRefGoogle Scholar
  54. Jeffrey M and Halliday W (1994) Numbers of neurons in vacuolated and non vacuolated neuroanatomical nuclei in bovine spongiform encephalopathy affected brains. J Comp Pathol 110: 287–293PubMedCrossRefGoogle Scholar
  55. Jeffrey M, Halliday W, Goodsir C (1992) A morphometric and immunohistochemical study of the vestibular nuclear complex in bovine spongiform encephalopathy. Acta Neuropathol 84: 651–657PubMedGoogle Scholar
  56. Jeffrey M, Begara-McGorum I, Clark S, Martin S, Clark J, Chaplin M and Gonzalez L (2002) Occurrence and Distribution of Infection-specific PrP in Tissues of Clinical Scrapie Cases and Cull Sheep from Scrapie-affected Farms in Shetland. J Comp Pathol 127: 264–273PubMedCrossRefGoogle Scholar
  57. Jeffrey M, Martin S, Thomson JR, Dingwall WS, BegaraMcGorum I and Gonzalez L (2001a) Onset and distribution of tissue PrP accumulation in scrapie-affected Suffolk sheep as demonstrated by sequential necropsies and tonsillar biopsies. J Comp Pathol 125: 48–57PubMedCrossRefGoogle Scholar
  58. Jeffrey M, McGovern G, Goodsir CM, Brown KL and Bruce ME (2000) Sites of prion protein accumulation in scrapie-infected mouse spleen revealed by immuno-electron microscopy. J Pathol 191: 323–332PubMedCrossRefGoogle Scholar
  59. Jeffrey M, Ryder S, Martin S, Hawkins SAC, Terry L, Berthelin Baker C and Bellworthy SJ (2001b) Oral inoculation of sheep with the agent of bovine spongiform encephalopathy (BSE) 1. Onset and distribution of disease-specific PrP accumulation in brain and viscera. J Comp Pathol 124: 280–289Google Scholar
  60. Jeffrey M and Wells GA (1988) Spongiform encephalopathy in a nyala (Tragelaphus angasi) Vet Pathol 25: 398–399CrossRefGoogle Scholar
  61. Jeffrey M, Martin S, Gonzalez L (2003) Cell-associated variants of disease-specific PrP immunolabelling are found in different sources of sheep transmissible spongiform encephalopathy. J Gen Virol 84: 1033–1046PubMedCrossRefGoogle Scholar
  62. Kimberlin RF and Walker CA (1979) Pathogenesis of mouse scrapie: effect of route of inoculation on infectivity titres and dose response curves. J Comp Pathol 89: 39–47CrossRefGoogle Scholar
  63. Ligios C, Jeffrey M, Ryder SJ, Bellworthy SJ and Simmons M (2002) Distinction of scrapie phenotypes in sheep by lesion profiling. J Comp Pathol 127: 45–57PubMedCrossRefGoogle Scholar
  64. Mackenzie A (1983) Immunohistochemical demonstration of glial fibrillary acidic protein in scrapie. J Comp Pathol 93: 251–259PubMedCrossRefGoogle Scholar
  65. McBride PA, Schulz-Schaeffer WJ, Donaldson M, Bruce M, Diringer H, Kretzschmar HA and Beekes M (2001) Early spread of scrapie from the gastrointestinal tract to the central nervous system involves autonomic fibers of the splanchnic and vagus nerves. J Virol 75: 9320–9327PubMedCrossRefGoogle Scholar
  66. McGill I and Wells GAH (1993) Neuropathological findings in cattle with clinically suspect but histologically unconfirmed bovine spongiform encephalopathy (BSE)J Comp Pathol 108: 241–260PubMedGoogle Scholar
  67. Mohri S, Farquhar CF, Somerville RA, Jeffrey M, Foster J and Hope J (1992) Immunodetection of a disease specific PrP fraction in scrapie-affected sheep and BSE-affected cattle. Vet Rec 131: 537–539PubMedGoogle Scholar
  68. Moynagh J and Schimmel H (1999) Tests for BSE evaluated. Nature 400:105 Nathanson N, Wilesmith J, Wells GA and Griot C (1999) Bovine spongiform encephalopathy and related diseases. In: Prusiner SB (ed) Prion Biology and Diseases. Cold Spring Harbor Laboratory Press, Plainview, NY, pp 431–463Google Scholar
  69. Parchi P, Castellani R, Capellari S, Ghetti B, Young K, Chen SG, Farlow M, Dickson DW, Sima AAF, Trojanowski JQ, Petersen RB and Gambetti P (1996) Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease. Ann Neurol 39: 767–778PubMedCrossRefGoogle Scholar
  70. Parchi P, Chen SG, Brown P, Zou WQ, Capellari S, Budka H, Hainfellner J, Reyes PF, Golden GT, Hauw JJ, Gajdusek DC and Gambetti P (1998) Different patterns of truncated prion protein fragments correlate with distinct phenotypes in P102L Gerstmann-Straussler-Scheinker disease. PNAS 95: 8322–8327PubMedCrossRefGoogle Scholar
  71. Pathology and Pathogenesis of Bovine Spongiform Encephalopathy and Scrapie 95Google Scholar
  72. Prince MJ, Bailey JA, Barrowman PR, Bishop KJ, Campbell GR, and Wood IM (2003)Google Scholar
  73. Bovine Spongiform encephalopathy. Rev sci tech Off int Epiz 22:37–55Google Scholar
  74. Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216: 136–144PubMedCrossRefGoogle Scholar
  75. Prusiner SB (1999a) An introduction to prion biology and diseases. In: Prusiner SB (ed) Prion Biology and Diseases. Cold Spring Harbor Laboratory Press, Plainview, NY, pp 1–66Google Scholar
  76. Prusiner SB (1999b) Development of the prion concept. In: Prusiner SB (ed) Prion Biology and Diseases. Cold Spring Harbor Laboratory Press, Plainview, NY, pp 67–112Google Scholar
  77. Race R, Jenny A, Sutton D (1998) Scrapie Infectivity and Proteinase K-Resistant Prion Protein in Sheep Placenta, Brain, Spleen, and Lymph-Node: Implications for Transmission and Antemortem Diagnosis. J Infect Dis 178: 949–953Google Scholar
  78. Robinson M (1993) Transmission studies with transmissible mink encephalopathy and bovine spongiform encephalopathy, and a survey of mink feeding practices. J Am Vet Med Assoc 204: 72Google Scholar
  79. Ryder S, Spencer YI, Bellerby PJ and March SA (2001) Immunohistochemical detection of PrP in the medulla oblongata of sheep:the spectrum of staining in normal and scrapie-affected sheep. Vet Rec 148: 7–13PubMedCrossRefGoogle Scholar
  80. Safar J, Wille H, Itrri V, Groth D, Serban H, Torchia M, Cohen FE and Prusiner SB (1998) Eight prion strains have PrPs` molecules with different conformations. Nature Med 4: 1157–1165PubMedCrossRefGoogle Scholar
  81. Schaller O, Fatzer R, Stack M, Clark J, Cooley W, Biffiger K, Egli S, Doherr M, Vandevelde M, Heim D, Oesch B and Moser M (1999) Validation of a Western immunoblotting procedure for bovine PrPSc detection and its use as a rapid surveillance method for the diagnosis of bovine spongiform encephalopathy (BSE) Acta Neuropathol 98: 437–443.Google Scholar
  82. Scott AC, Done SH, Venables C and Dawson M (1987) Detection of scrapie associated fibrils as an aid to the diagnosis of natural sheep scrapie. Vet Rec 120: 280–281PubMedCrossRefGoogle Scholar
  83. Simmons MM, Harris P, Jeffrey M, Meek SC, Blamire IWH and Wells GAH (1996) BSE in Great Britain: Consistency of the neurohistopathological findings in two random annual samples of clinically suspect cases. Vet Rec 138: 175–177Google Scholar
  84. Somerville RA (1999) Host and transmissible spongiform encephalopathy agent strain control glycosylation of PrP. J Gen Virol 80: 1865–1872PubMedGoogle Scholar
  85. Somerville RA, Birkett CR, Farquhar CF, Hunter N, Goldmann W, Dornan J, Grover D, Hennion RM, Percy C, Foster J and Jeffrey M (1997) Immunodetection of PrPSc in spleens of some scrapie-infected sheep but not BSE-infected cows. J Gen Virol 78: 2389–2396PubMedGoogle Scholar
  86. Stack MJ, Scott AC, Done SH and Dawson M (1993) Scrapie associated fibril detection on decomposed and fixed ovine brain material. Res Vet Sci 55: 173–178PubMedCrossRefGoogle Scholar
  87. Stack MJ, Keyes P, Scott AC (1996) The diagnosis of bovine spongiform encephalopathy and scrapie by the detection of fibrils and the abnormal protein isoform. In: Baker HF, Ridley RM (eds) Prion Diseases. Humana Press Inc, Totowa, NJ, pp 85103Google Scholar
  88. Stack M, Chaplin M, Clark J (2002) Differentiation of prion protein glycoforms from naturally occurring sheep scrapie, sheep-passaged scrapie strains (CH1641 and SSBP1), bovine spongiform encephalopathy ( BSE) cases and Romney and Cheviot sheep experimentally inoculated with BSE using two monoclonal antibodies. Acta Neuropathol 104: 279–286Google Scholar
  89. Telling GC, Haga T, Torchia M, Tremblay P, DeArmond SJ and Prusiner SB (1996) Interactions between wild-type and mutant prion proteins modulate neurodegeneration transgenic mice. Genes and Dev 10: 1736–1750PubMedCrossRefGoogle Scholar
  90. Terry L, Marsh S, Ryder SJ, Hawkins SAC, Wells GAH and Spencer YI (2003) Detection of disease-specific PrP in the distal ileum of cattle orally exposed to the BSE agent. Vet Rec 152: 387–392PubMedCrossRefGoogle Scholar
  91. Theil D, Fatzer R, Meyer R, Schobesberger M, Zurbriggen A, Vandevelde M (1999) Nuclear DNA fragmentation and immune reactivity in bovine spongiform encephalopathy. J Comp Pathol 121: 357–367PubMedCrossRefGoogle Scholar
  92. Vankeulen LJM, Schreuder BEC, Meloen RH, Mooijharkes G, Vromans MEW and Langeveld JPM (1996) Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie. J Clin Micro 34: 1228–1231Google Scholar
  93. Vankeulen LJM, Schreuder BEC, Meloen RH, Poelenvandenberg M, Mooijharkes G, Vromans MEW and Langeveld JPM (1995) Immunohistochemical Detection and Localization of Prion Protein in Brain-Tissue of Sheep with Natural Scrapie. Vet Pathol 32: 299–308CrossRefGoogle Scholar
  94. Vankeulen LJM, Schreuder BEC, Vromans MEW, Langeveld JPM and Smits MA (1999) Scrapie-associated prion protein in the gastrointestinal tract of sheep with natural scrapie. J Comp Pathol 121: 55–63CrossRefGoogle Scholar
  95. Vankeulen LJM, Schreuder BEC, Vromans MEW, Langeveld JPM and Smits MA (2000) Pathogenesis of natural scrapie in sheep. Archives of Virology suppl 16: 57–71Google Scholar
  96. Weissmann C (1992) How can the `protein only’ hypothesis of prion propagation be reconciled with the existence of multiple prion strain? Prion diseases of humans and animals (edited by Prusiner, S B; Collinge, J; Powell, J; Anderton, B) Ellis Horwood Limited, Chichester, UK, 523–530Google Scholar
  97. Wells GAH, Dawson M, Hawkins SAC, Green RB, Dexter I, Francis ME, Simmons MM, Austin AR and Horigan MW (1994) Infectivity in the ileum of cattle challenged orally with bovine spongiform encephalopathy. Vet Rec 135: 40–41PubMedCrossRefGoogle Scholar
  98. Wells GAH, Hancock RD, Cooley WA, Richards MS, Higgins RJ and David GP (1989) Bovine Spongiform Encephalopathy: Diagnostic Significance of Vacuolar Changes in Selected Nuclei of the Medulla Oblongata. Vet Rec125: 521–524Google Scholar
  99. Wells GAH, Hawkins SAC, Green RB, Austin AR, Dexter I, Spencer YI, Chaplin MJ, Stack MJ and Dawson M (1998) Preliminary Observations on the Pathogenesis of Experimental Bovine Spongiform Encephalopathy (BSE): An Update. Vet Rec 142: 103–106Google Scholar
  100. Wells GAH, Hawkins SAC, Green RB, Spencer YI, Dexter I and Dawson M (1999) Limited detection of sternal bone marrow infectivity in the clinical phase of experimental bovine spongiform encephalopathy (BSE) Vet Rec 144: 292–294PubMedGoogle Scholar
  101. Wells GAH, Hawkins SAC, Hadlow WJ, Spencer YI (1992) The discovery of bovine spongiform encephalopathy and observations on the vacuolar changes Prion diseases of humans and animals (edited by Prusiner SB, Collinge J, Powell J, Anderton B)Ellis Horwood, LondonGoogle Scholar
  102. Wells GAH and McGill IS (1992) Recently described scrapie-like encephalopathies of animals: case definitions. Res Vet Sci 53: 1–10PubMedCrossRefGoogle Scholar
  103. Pathology and Pathogenesis of Bovine Spongiform Encephalopathy and Scrapie 97Google Scholar
  104. Wells GAH, Scott AC, Johnson CT, Gunning RF, Hancock RD, Jeffrey M, Dawson M and Bradley M (1987) A novel progressive spongiform encephalopathy in cattle. Vet Rec 121: 419–420PubMedCrossRefGoogle Scholar
  105. Wells GAH and Simmons MM (1996) The essential lesion profile of bovine spongiform encephalopathy (BSE) in cattle is unaffected by breed or route of infection. Neuropathol Appl Neurobiol 22: 453Google Scholar
  106. Wells GAH and Wilesmith JW (1995) The neuropathology and epidemiology of bovine spongiform encephalopathy. Brain Path 5: 91–103CrossRefGoogle Scholar
  107. Wells G, Scott A, Wilesmith J, Simmons M and Matthews D (1994) Correlation between the results of a histopathological examination and the detection of abnormal brain fibrils in the diagnosis of bovine spongiform encephalopathy. Res Vet Sci 56: 346–351PubMedCrossRefGoogle Scholar
  108. Wilesmith JW, Ryan JM, Atkinson MJ (1991) Bovine Spongiform Encephalopathy: Epidemiological Studies on the Origin. Vet Rec 128: 199–203Google Scholar
  109. Willoughby K, Kelly DF, Lyon DG and Wells GAH (1992) Spongiform encephalopathy in a captive puma (Felis concolor) Vet Rec 131: 431–434Google Scholar
  110. Wyatt IM, Pearson GR, Smerdon T, Gruffydd-Jones TJ, Wells GAH (1990) Spongiform Encephalopathy in a Cat. Vet Rec 20: 513Google Scholar
  111. Zlotnik I (1962) The pathology of scrapie:a comparative study of lesions in the brain of sheep and goats. Acta Neuropathol: Suppl 1: 61–70Google Scholar
  112. Zlotnik I, Rennie JC (1958) A comparative study of the incidence of vacuolated neurones in the medulla from apparently healthy sheep of various breeds. J Comp Path Therap 68: 411–415Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • M. Jeffrey
    • 1
  • L. González
    • 1
  1. 1.Veterinary Laboratories Agency (VLA-Lasswade)Bush Loan, Penicuik, MidlothianUK

Personalised recommendations