Transgenic Mouse Models and Prion Strains

  • Glenn C. TellingEmail author
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 305)


Here we review the known strain profiles of various prion diseases of animals and humans, and how transgenic mouse models are being used to elucidate basic molecular mechanisms of prion propagation and strain variation and for assessing the zoonotic potential of various animal prion strains.


Quasi-species Species barriers Strains Transgenic models 


  1. 1.
    Bruce ME, McBride PA, Farquhar CF (1989) Precise targeting of the pathology of the sialoglycoprotein, PrP, and vacuolar degeneration in mouse scrapie. Neurosci Lett 102:1–6CrossRefGoogle Scholar
  2. 2.
    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 71–86Google Scholar
  3. 3.
    Dickinson AG, Meikle VMH (1971) Host-genotype and agent effects in scrapie incubation: change in allelic interaction with different strains of agent. Mol Gen Genet 112:73–79CrossRefGoogle Scholar
  4. 4.
    Bruce ME (1993) Scrapie strain variation and mutation. Br Med Bull 49:822–838Google Scholar
  5. 5.
    Westaway D, Goodman PA, Mirenda CA, McKinley MP, Carlson GA, Prusiner SB (1987) Distinct prion proteins in short and long scrapie incubation period mice. Cell 51:651–662CrossRefGoogle Scholar
  6. 6.
    Agrimi U, Nonno R, Dell’Omo G, Di Bari MA, Conte M, Chiappini B, Esposito E, Di Guardo G, Windl O, Vaccari G, Lipp HP (2008) Prion protein amino acid determinants of differential susceptibility and molecular feature of prion strains in mice and voles. PLoS Pathog 4:e1000113CrossRefGoogle Scholar
  7. 7.
    Bessen RA, Marsh RF (1992) Identification of two biologically distinct strains of transmissible mink encephalopathy in hamsters. J Gen Virol 73:329–334CrossRefGoogle Scholar
  8. 8.
    Pattison IH (1965) 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. U.S. Government Printing, Washington, DC, pp 249–257Google Scholar
  9. 9.
    Bartz JC, Marsh RF, McKenzie DI, Aiken JM (1998) The host range of chronic wasting disease is altered on passage in ferrets. Virology 251:297–301CrossRefGoogle Scholar
  10. 10.
    Prusiner SB, Scott M, Foster D, Pan K-M, Groth D, Mirenda C, Torchia M, Yang S-L, Serban D, Carlson GA, Hoppe PC, Westaway D, DeArmond SJ (1990) Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63:673–686CrossRefGoogle Scholar
  11. 11.
    Scott M, Groth D, Foster D, Torchia M, Yang S-L, DeArmond SJ, Prusiner SB (1993) Propagation of prions with artificial properties in transgenic mice expressing chimeric PrP genes. Cell 73:979–988CrossRefGoogle Scholar
  12. 12.
    Kocisko DA, Come JH, Priola SA, Chesebro B, Raymond GJ, Lansbury PT Jr, Caughey B (1994) Cell-free formation of protease-resistant prion protein. Nature 370:471–474CrossRefGoogle Scholar
  13. 13.
    Hunter N, Goldmann W, Marshall E, O’Neill G (2000) Sheep and goats: natural and experimental TSEs and factors influencing incidence of disease. Arch Virol Suppl 181–188Google Scholar
  14. 14.
    Baker HF, Poulter M, Crow TJ, Frith CD, Lofthouse R, Ridley RM (1991) Amino acid polymorphism in human prion protein and age at death in inherited prion disease. Lancet 337:1286CrossRefGoogle Scholar
  15. 15.
    Collinge J, Palmer MS, Dryden AJ (1991) Genetic predisposition to iatrogenic Creutzfeldt–Jakob disease. Lancet 337:1441–1442CrossRefGoogle Scholar
  16. 16.
    Palmer MS, Dryden AJ, Hughes JT, Collinge J (1991) Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob disease. Nature 352:340–342CrossRefGoogle Scholar
  17. 17.
    Scott M, Foster D, Mirenda C, Serban D, Coufal F, Wälchli M, Torchia M, Groth D, Carlson G, DeArmond SJ, Westaway D, Prusiner SB (1989) Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques. Cell 59:847–857CrossRefGoogle Scholar
  18. 18.
    Büeler H, Fischer M, Lang Y, Bluethmann H, Lipp H-P, DeArmond SJ, Prusiner SB, Aguet M, Weissmann C (1992) Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356:577–582CrossRefGoogle Scholar
  19. 19.
    Telling GC, Scott M, Hsiao KK, Foster D, Yang SL, Torchia M, Sidle KC, Collinge J, DeArmond SJ, Prusiner SB (1994) Transmission of Creutzfeldt–Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein. Proc Natl Acad Sci USA 91:9936–9940CrossRefGoogle Scholar
  20. 20.
    Telling GC, Scott M, Mastrianni J, Gabizon R, Torchia M, Cohen FE, DeArmond SJ, Prusiner SB (1995) Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell 83:79–90CrossRefGoogle Scholar
  21. 21.
    Telling GC, Haga T, Torchia M, Tremblay P, DeArmond SJ, Prusiner SB (1996) Interactions between wild-type and mutant prion proteins modulate neurodegeneration in transgenic mice. Genes Dev 10:1736–1750CrossRefGoogle Scholar
  22. 22.
    Chiesa R, Piccardo P, Ghetti B, Harris DA (1998) Neurological illness in transgenic mice expressing a prion protein with an insertional mutation. Neuron 21:1339–1351CrossRefGoogle Scholar
  23. 23.
    Gombojav A, Shimauchi I, Horiuchi M, Ishiguro N, Shinagawa M, Kitamoto T, Miyoshi I, Mohri S, Takata M (2003) Susceptibility of transgenic mice expressing chimeric sheep, bovine and human PrP genes to sheep scrapie. J Vet Med Sci 65:341–347CrossRefGoogle Scholar
  24. 24.
    Kupfer L, Eiden M, Buschmann A, Groschup MH (2007) Amino acid sequence and prion strain specific effects on the in vitro and in vivo convertibility of ovine/murine and bovine/murine prion protein chimeras. Biochim Biophys Acta 1772:704–713CrossRefGoogle Scholar
  25. 25.
    Scott MR, Safar J, Telling G, Nguyen O, Groth D, Torchia M, Koehler R, Tremblay P, Walther D, Cohen FE, DeArmond SJ, Prusiner SB (1997) Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice. Proc Natl Acad Sci USA 94:14279–14284CrossRefGoogle Scholar
  26. 26.
    Telling GC (2010) Nucleic acid-free mutation of prion strains. Prion 4:252–255CrossRefGoogle Scholar
  27. 27.
    Bishop MT, Hart P, Aitchison L, Baybutt HN, Plinston C, Thomson V, Tuzi NL, Head MW, Ironside JW, Will RG, Manson JC (2006) Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 5:393–398CrossRefGoogle Scholar
  28. 28.
    Asante EA, Linehan JM, Desbruslais M, Joiner S, Gowland I, Wood AL, Welch J, Hill AF, Lloyd SE, Wadsworth JD, Collinge J (2002) BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J 21:6358–6366CrossRefGoogle Scholar
  29. 29.
    Clouscard C, Beaudry P, Elsen JM, Milan D, Dussaucy M, Bounneau C, Schelcher F, Chatelain J, Launay JM, Laplanche JL (1995) Different allelic effects of the codons 136 and 171 of the prion protein gene in sheep with natural scrapie. J Gen Virol 76(Pt 8):2097–2101CrossRefGoogle Scholar
  30. 30.
    Hunter N, Foster JD, Goldmann W, Stear MJ, Hope J, Bostock C (1996) Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes. Arch Virol 141:809–824CrossRefGoogle Scholar
  31. 31.
    Westaway D, Zuliani V, Cooper CM, Da Costa M, Neuman S, Jenny AL, Detwiler L, Prusiner SB (1994) Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie. Genes Dev 8:959–969CrossRefGoogle Scholar
  32. 32.
    Hunter N, Goldmann W, Foster JD, Cairns D, Smith G (1997) Natural scrapie and PrP genotype: case-control studies in British sheep. Vet Rec 141:137–140CrossRefGoogle Scholar
  33. 33.
    Bruce ME (2003) TSE strain variation. Br Med Bull 66:99–108CrossRefGoogle Scholar
  34. 34.
    Bruce ME, Dickinson AG (1987) Biological evidence that the scrapie agent has an independent genome. J Gen Virol 68:79–89CrossRefGoogle Scholar
  35. 35.
    Dickinson AG (1976) Scrapie in sheep and goats. In: Kimberlin RH (ed) Slow virus diseases of animals and man. North-Holland Publishing, Amsterdam, pp 209–241Google Scholar
  36. 36.
    Bruce ME, Boyle A, Cousens S, McConnell I, Foster J, Goldmann W, Fraser H (2002) Strain characterization of natural sheep scrapie and comparison with BSE. J Gen Virol 83:695–704Google Scholar
  37. 37.
    Benestad SL, Sarradin P, Thu B, Schonheit J, Tranulis MA, Bratberg B (2003) Cases of scrapie with unusual features in Norway and designation of a new type, Nor98. Vet Rec 153:202–208CrossRefGoogle Scholar
  38. 38.
    Simmons MM, Konold T, Simmons HA, Spencer YI, Lockey R, Spiropoulos J, Everitt S, Clifford D (2007) Experimental transmission of atypical scrapie to sheep. BMC Vet Res 3:20CrossRefGoogle Scholar
  39. 39.
    Everest SJ, Thorne L, Barnicle DA, Edwards JC, Elliott H, Jackman R, Hope J (2006) Atypical prion protein in sheep brain collected during the British scrapie-surveillance programme. J Gen Virol 87:471–477CrossRefGoogle Scholar
  40. 40.
    Luhken G, Buschmann A, Brandt H, Eiden M, Groschup MH, Erhardt G (2007) Epidemiological and genetical differences between classical and atypical scrapie cases. Vet Res 38:65–80CrossRefGoogle Scholar
  41. 41.
    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 102:16031–16036CrossRefGoogle Scholar
  42. 42.
    Crozet C, Bencsik A, Flamant F, Lezmi S, Samarut J, Baron T (2001) Florid plaques in ovine PrP transgenic mice infected with an experimental ovine BSE. EMBO Rep 2:952–956CrossRefGoogle Scholar
  43. 43.
    Crozet C, Flamant F, Bencsik A, Aubert D, Samarut J, Baron T (2001) Efficient transmission of two different sheep scrapie isolates in transgenic mice expressing the ovine PrP gene. J Virol 75:5328–5334CrossRefGoogle Scholar
  44. 44.
    Vilotte JL, Soulier S, Essalmani R, Stinnakre MG, Vaiman D, Lepourry L, Da Silva JC, Besnard N, Dawson M, Buschmann A, Groschup M, Petit S, Madelaine MF, Rakatobe S, Le Dur A, Vilette D, Laude H (2001) Markedly increased susceptibility to natural sheep scrapie of transgenic mice expressing ovine PrP. J Virol 75:5977–5984CrossRefGoogle Scholar
  45. 45.
    Thackray AM, Hopkins L, Spiropoulos J, Bujdoso R (2008) Molecular and transmission characteristics of primary-passaged ovine scrapie isolates in conventional and ovine PrP transgenic mice. J Virol 82:11197–11207CrossRefGoogle Scholar
  46. 46.
    Tixador P, Herzog L, Reine F, Jaumain E, Chapuis J, Le Dur A, Laude H, Beringue V (2010) The physical relationship between infectivity and prion protein aggregates is strain-dependent. PLoS Pathog 6:e1000859CrossRefGoogle Scholar
  47. 47.
    Baron T, Biacabe AG (2007) Molecular behaviors of “CH1641-like” sheep scrapie isolates in ovine transgenic mice (TgOvPrP4). J Virol 81:7230–7237CrossRefGoogle Scholar
  48. 48.
    Baron T, Crozet C, Biacabe AG, Philippe S, Verchere J, Bencsik A, Madec JY, Calavas D, Samarut J (2004) Molecular analysis of the protease-resistant prion protein in scrapie and bovine spongiform encephalopathy transmitted to ovine transgenic and wild-type mice. J Virol 78:6243–6251CrossRefGoogle Scholar
  49. 49.
    Eloit M, Adjou K, Coulpier M, Fontaine JJ, Hamel R, Lilin T, Messiaen S, Andreoletti O, Baron T, Bencsik A, Biacabe AG, Beringue V, Laude H, Le Dur A, Vilotte JL, Comoy E, Deslys JP, Grassi J, Simon S, Lantier F, Sarradin P (2005) BSE agent signatures in a goat. Vet Rec 156:523–524Google Scholar
  50. 50.
    Jeffrey M, Martin S, Gonzalez L, Foster J, Langeveld JP, van Zijderveld FG, Grassi J, Hunter N (2006) Immunohistochemical features of PrP(d) accumulation in natural and experimental goat transmissible spongiform encephalopathies. J Comp Pathol 134:171–181CrossRefGoogle Scholar
  51. 51.
    Jacobs JG, Langeveld JP, Biacabe AG, Acutis PL, Polak MP, Gavier-Widen D, Buschmann A, Caramelli M, Casalone C, Mazza M, Groschup M, Erkens JH, Davidse A, van Zijderveld FG, Baron T (2007) Molecular discrimination of atypical bovine spongiform encephalopathy strains from a geographical region spanning a wide area in Europe. J Clin Microbiol 45:1821–1829CrossRefGoogle Scholar
  52. 52.
    Casalone C, Zanusso G, Acutis P, Ferrari S, Capucci L, Tagliavini F, Monaco S, Caramelli M (2004) Identification of a second bovine amyloidotic spongiform encephalopathy: molecular similarities with sporadic Creutzfeldt–Jakob disease. Proc Natl Acad Sci USA 101:3065–3070CrossRefGoogle Scholar
  53. 53.
    Richt JA, Hall SM (2008) BSE case associated with prion protein gene mutation. PLoS Pathog 4:e1000156CrossRefGoogle Scholar
  54. 54.
    Buschmann A, Groschup MH (2005) Highly bovine spongiform encephalopathy-sensitive transgenic mice confirm the essential restriction of infectivity to the nervous system in clinically diseased cattle. J Infect Dis 192:934–942CrossRefGoogle Scholar
  55. 55.
    Castilla J, Gutierrez Adan A, Brun A, Pintado B, Ramirez MA, Parra B, Doyle D, Rogers M, Salguero FJ, Sanchez C, Sanchez-Vizcaino JM, Torres JM (2003) Early detection of PrPres in BSE-infected bovine PrP transgenic mice. Arch Virol 148:677–691CrossRefGoogle Scholar
  56. 56.
    Scott MR, Will R, Ironside J, Nguyen H-OB, Tremblay P, DeArmond SJ, Prusiner SB (1999) Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc Natl Acad Sci USA 96(26):15137–15142CrossRefGoogle Scholar
  57. 57.
    Beringue V, Andreoletti O, Le Dur A, Essalmani R, Vilotte JL, Lacroux C, Reine F, Herzog L, Biacabe AG, Baron T, Caramelli M, Casalone C, Laude H (2007) A bovine prion acquires an epidemic bovine spongiform encephalopathy strain-like phenotype on interspecies transmission. J Neurosci 27:6965–6971CrossRefGoogle Scholar
  58. 58.
    Beringue V, Bencsik A, Le Dur A, Reine F, Lai TL, Chenais N, Tilly G, Biacabe AG, Baron T, Vilotte JL, Laude H (2006) Isolation from cattle of a prion strain distinct from that causing bovine spongiform encephalopathy. PLoS Pathog 2:e112CrossRefGoogle Scholar
  59. 59.
    Buschmann A, Gretzschel A, Biacabe AG, Schiebel K, Corona C, Hoffmann C, Eiden M, Baron T, Casalone C, Groschup MH (2006) Atypical BSE in Germany–proof of transmissibility and biochemical characterization. Vet Microbiol 117:103–116CrossRefGoogle Scholar
  60. 60.
    Capobianco R, Casalone C, Suardi S, Mangieri M, Miccolo C, Limido L, Catania M, Rossi G, Di Fede G, Giaccone G, Bruzzone MG, Minati L, Corona C, Acutis P, Gelmetti D, Lombardi G, Groschup MH, Buschmann A, Zanusso G, Monaco S, Caramelli M, Tagliavini F (2007) Conversion of the BASE prion strain into the BSE strain: the origin of BSE? PLoS Pathog 3:e31CrossRefGoogle Scholar
  61. 61.
    Korth C, Kaneko K, Groth D, Heye N, Telling G, Mastrianni J, Parchi P, Gambetti P, Will R, Ironside J, Heinrich C, Tremblay P, DeArmond SJ, Prusiner SB (2003) Abbreviated incubation times for human prions in mice expressing a chimeric mouse-human prion protein transgene. Proc Natl Acad Sci USA 100:4784–4789CrossRefGoogle Scholar
  62. 62.
    Wadsworth JD, Asante EA, Desbruslais M, Linehan JM, Joiner S, Gowland I, Welch J, Stone L, Lloyd SE, Hill AF, Brandner S, Collinge J (2004) Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science 306:1793–1796CrossRefGoogle Scholar
  63. 63.
    Beringue V, Herzog L, Reine F, Le Dur A, Casalone C, Vilotte JL, Laude H (2008) Transmission of atypical bovine prions to mice transgenic for human prion protein. Emerg Infect Dis 14:1898–1901CrossRefGoogle Scholar
  64. 64.
    Kong Q, Zheng M, Casalone C, Qing L, Huang S, Chakraborty B, Wang P, Chen F, Cali I, Corona C, Martucci F, Iulini B, Acutis P, Wang L, Liang J, Wang M, Li X, Monaco S, Zanusso G, Zou WQ, Caramelli M, Gambetti P (2008) Evaluation of the human transmission risk of an atypical bovine spongiform encephalopathy prion strain. J Virol 82:3697–3701CrossRefGoogle Scholar
  65. 65.
    Beringue V, Le Dur A, Tixador P, Reine F, Lepourry L, Perret-Liaudet A, Haik S, Vilotte JL, Fontes M, Laude H (2008) Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD. PLoS ONE 3:e1419CrossRefGoogle Scholar
  66. 66.
    Williams ES, Young S (1992) Spongiform encephalopathies in Cervidae. Rev Sci Tech 11:551–567Google Scholar
  67. 67.
    Browning SR, Mason GL, Seward T, Green M, Eliason GA, Mathiason C, Miller MW, Williams ES, Hoover E, Telling GC (2004) Transmission of prions from mule deer and elk with chronic wasting disease to transgenic mice expressing cervid PrP. J Virol 78:13345–13350CrossRefGoogle Scholar
  68. 68.
    Marsh RF, Kincaid AE, Bessen RA, Bartz JC (2005) Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus). J Virol 79:13794–13796CrossRefGoogle Scholar
  69. 69.
    Sigurdson CJ, Mathiason CK, Perrott MR, Eliason GA, Spraker TR, Glatzel M, Manco G, Bartz JC, Miller MW, Hoover EA (2008) Experimental chronic wasting disease (CWD) in the ferret. J Comp Pathol 138:189–196CrossRefGoogle Scholar
  70. 70.
    Angers RC, Seward TS, Napier D, Green M, Hoover EA, Spraker T, O’Rourke K, Balachandran A, Telling GC (2009) Prions in antler velvet of CWD-infected elk. Emerg Infect Dis 15:696–703CrossRefGoogle Scholar
  71. 71.
    Green KM, Browning SR, Seward TS, Jewell JE, Ross DL, Green MA, Williams ES, Hoover EA, Telling GC (2008) The elk PRNP codon 132 polymorphism controls cervid and scrapie prion propagation. J Gen Virol 89:598–608CrossRefGoogle Scholar
  72. 72.
    Kong Q, Huang S, Zou W, Vanegas D, Wang M, Wu D, Yuan J, Zheng M, Bai H, Deng H, Chen K, Jenny AL, O’Rourke K, Belay ED, Schonberger LB, Petersen RB, Sy MS, Chen SG, Gambetti P (2005) Chronic wasting disease of elk: transmissibility to humans examined by transgenic mouse models. J Neurosci 25:7944–7949CrossRefGoogle Scholar
  73. 73.
    LaFauci G, Carp RI, Meeker HC, Ye X, Kim JI, Natelli M, Cedeno M, Petersen RB, Kascsak R, Rubenstein R (2006) Passage of chronic wasting disease prion into transgenic mice expressing rocky mountain elk (Cervus elaphus nelsoni) PrPC. J Gen Virol 87:3773–3780CrossRefGoogle Scholar
  74. 74.
    Meade-White K, Race B, Trifilo M, Bossers A, Favara C, Lacasse R, Miller M, Williams E, Oldstone M, Race R, Chesebro B (2007) Resistance to chronic wasting disease in transgenic mice expressing a naturally occurring allelic variant of deer prion protein. J Virol 81:4533–4539CrossRefGoogle Scholar
  75. 75.
    Tamguney G, Giles K, Bouzamondo-Bernstein E, Bosque PJ, Miller MW, Safar J, DeArmond SJ, Prusiner SB (2006) Transmission of elk and deer prions to transgenic mice. J Virol 80:9104–9114CrossRefGoogle Scholar
  76. 76.
    Trifilo MJ, Ying G, Teng C, Oldstone MB (2007) Chronic wasting disease of deer and elk in transgenic mice: oral transmission and pathobiology. Virology 365:136–143CrossRefGoogle Scholar
  77. 77.
    Haley NJ, Mathiason CK, Zabel MD, Telling GC, Hoover EA (2009) Detection of sub-clinical CWD infection in conventional test-negative deer long after oral exposure to urine and feces from CWD+ deer. PLoS ONE 4:e7990CrossRefGoogle Scholar
  78. 78.
    Haley NJ, Seelig DM, Zabel MD, Telling GC, Hoover EA (2009) Detection of CWD prions in urine and saliva of deer by transgenic mouse bioassay. PLoS ONE 4:e4848CrossRefGoogle Scholar
  79. 79.
    Mathiason CK, Powers JG, Dahmes SJ, Osborn DA, Miller KV, Warren RJ, Mason GL, Hays SA, Hayes-Klug J, Seelig DM, Wild MA, Wolfe LL, Spraker TR, Miller MW, Sigurdson CJ, Telling GC, Hoover EA (2006) Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 314:133–136CrossRefGoogle Scholar
  80. 80.
    Tamguney G, Miller MW, Wolfe LL, Sirochman TM, Glidden DV, Palmer C, Lemus A, DeArmond SJ, Prusiner SB (2009) Asymptomatic deer excrete infectious prions in faeces. Nature 461:529–532CrossRefGoogle Scholar
  81. 81.
    Jewell JE, Conner MM, Wolfe LL, Miller MW, Williams ES (2005) Low frequency of PrP genotype 225SF among free-ranging mule deer (Odocoileus hemionus) with chronic wasting disease. J Gen Virol 86:2127–2134CrossRefGoogle Scholar
  82. 82.
    Johnson C, Johnson J, Clayton M, McKenzie D, Aiken J (2003) Prion protein gene heterogeneity in free-ranging white-tailed deer within the chronic wasting disease affected region of Wisconsin. J Wildl Dis 39:576–581CrossRefGoogle Scholar
  83. 83.
    Raymond GJ, Bossers A, Raymond LD, O’Rourke KI, McHolland LE, Bryant PK 3rd, Miller MW, Williams ES, Smits M, Caughey B (2000) Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease. EMBO J 19:4425–4430CrossRefGoogle Scholar
  84. 84.
    Heaton MP, Leymaster KA, Freking BA, Hawk DA, Smith TP, Keele JW, Snelling WM, Fox JM, Chitko-McKown CG, Laegreid WW (2003) Prion gene sequence variation within diverse groups of U.S. sheep, beef cattle, and deer. Mamm Genome 14:765–777CrossRefGoogle Scholar
  85. 85.
    O’Rourke KI, Spraker TR, Hamburg LK, Besser TE, Brayton KA, Knowles DP (2004) Polymorphisms in the prion precursor functional gene but not the pseudogene are associated with susceptibility to chronic wasting disease in white-tailed deer. J Gen Virol 85:1339–1346CrossRefGoogle Scholar
  86. 86.
    O’Rourke KI, Baszler TV, Miller JM, Spraker TR, Sadler-Riggleman I, Knowles DP (1998) Monoclonal antibody F89/160.1.5 defines a conserved epitope on the ruminant prion protein. J Clin Microbiol 36:1750–1755Google Scholar
  87. 87.
    Schatzl HM, Wopfner F, Gilch S, von Brunn A, Jager G (1997) Is codon 129 of prion protein polymorphic in human beings but not in animals? Lancet 349:1603–1604CrossRefGoogle Scholar
  88. 88.
    O’Rourke KI, Besser TE, Miller MW, Cline TF, Spraker TR, Jenny AL, Wild MA, Zebarth GL, Williams ES (1999) PrP genotypes of captive and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease. J Gen Virol 80(Pt 10):2765–2769Google Scholar
  89. 89.
    Hamir AN, Gidlewski T, Spraker TR, Miller JM, Creekmore L, Crocheck M, Cline T, O’Rourke KI (2006) Preliminary observations of genetic susceptibility of elk (Cervus elaphus nelsoni) to chronic wasting disease by experimental oral inoculation. J Vet Diagn Invest 18:110–114CrossRefGoogle Scholar
  90. 90.
    O’Rourke KI, Spraker TR, Zhuang D, Greenlee JJ, Gidlewski TE, Hamir AN (2007) Elk with a long incubation prion disease phenotype have a unique PrPd profile. Neuroreport 18:1935–1938CrossRefGoogle Scholar
  91. 91.
    Green KM, Castilla J, Seward TS, Napier DL, Jewell JE, Soto C, Telling GC (2008) Accelerated high fidelity prion amplification within and across prion species barriers. PLoS Pathog 4:e1000139CrossRefGoogle Scholar
  92. 92.
    Angers RC, Kang HE, Napier D, Browning S, Seward T, Mathiason C, Balachandran A, McKenzie D, Castilla J, Soto C, Jewell J, Graham C, Hoover EA, Telling GC (2010) Prion strain mutation determined by prion protein conformational compatibility and primary structure. Science 328:1154–1158CrossRefGoogle Scholar
  93. 93.
    Johnson C, Johnson J, Vanderloo JP, Keane D, Aiken JM, McKenzie D (2006) Prion protein polymorphisms in white-tailed deer influence susceptibility to chronic wasting disease. J Gen Virol 87:2109–2114CrossRefGoogle Scholar
  94. 94.
    Sigurdson CJ, Manco G, Schwarz P, Liberski P, Hoover EA, Hornemann S, Polymenidou M, Miller MW, Glatzel M, Aguzzi A (2006) Strain fidelity of chronic wasting disease upon murine adaptation. J Virol 80:12303–12311CrossRefGoogle Scholar
  95. 95.
    Raymond GJ, Raymond LD, Meade-White KD, Hughson AG, Favara C, Gardner D, Williams ES, Miller MW, Race RE, Caughey B (2007) Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains. J Virol 81:4305–4314CrossRefGoogle Scholar
  96. 96.
    Belay ED, Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB (2004) Chronic wasting disease and potential transmission to humans. Emerg Infect Dis 10:977–984CrossRefGoogle Scholar
  97. 97.
    Mawhinney S, Pape WJ, Forster JE, Anderson CA, Bosque P, Miller MW (2006) Human prion disease and relative risk associated with chronic wasting disease. Emerg Infect Dis 12:1527–1535CrossRefGoogle Scholar
  98. 98.
    Sandberg M, Al-Doujaily H, Sigurdson C, Glatzel M, O’Malley C, Powell C, Asante EA, Linehan JM, Brandner S, Wadsworth JD, Collinge J (2010) Chronic wasting disease prions are not transmissible to transgenic mice over-expressing human prion protein. J Gen Virol 91:2651–2657CrossRefGoogle Scholar
  99. 99.
    Race B, Meade-White KD, Miller MW, Barbian KD, Rubenstein R, LaFauci G, Cervenakova L, Favara C, Gardner D, Long D, Parnell M, Striebel J, Priola SA, Ward A, Williams ES, Race R, Chesebro B (2009) Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis 15:1366–1376CrossRefGoogle Scholar
  100. 100.
    Robinson MM, Hadlow WJ, Huff TP, Wells GAH, Dawson M, Marsh RF, Gorham JR (1994) Experimental infection of mink with bovine spongiform encephalopathy. J Gen Virol 75:2151–2155CrossRefGoogle Scholar
  101. 101.
    Marsh RF, Bessen RA, Lehmann S, Hartsough GR (1991) Epidemiological and experimental studies on a new incident of transmissible mink encephalopathy. J Gen Virol 72:589–594CrossRefGoogle Scholar
  102. 102.
    Hanson RP, Eckroade RJ, Marsh RF, ZuRhein GM, Kanitz CL, Gustafson DP (1971) Susceptibility of mink to sheep scrapie. Science 172:859–861CrossRefGoogle Scholar
  103. 103.
    Barlow RM, Rennie JC (1970) Transmission experiments with a scrapie-like encephalopathy of mink. J Comp Pathol 80:75–79CrossRefGoogle Scholar
  104. 104.
    Harrington RD, Baszler TV, O’Rourke KI, Schneider DA, Spraker TR, Liggitt HD, Knowles DP (2008) A species barrier limits transmission of chronic wasting disease to mink (Mustela vison). J Gen Virol 89:1086–1096CrossRefGoogle Scholar
  105. 105.
    Hamir AN, Kunkle RA, Miller JM, Bartz JC, Richt JA (2006) First and second cattle passage of transmissible mink encephalopathy by intracerebral inoculation. Vet Pathol 43:118–126CrossRefGoogle Scholar
  106. 106.
    Robinson MM, Hadlow WJ, Knowles DP, Huff TP, Lacy PA, Marsh RF, Gorham JR (1995) Experimental infection of cattle with the agents of transmissible mink encephalopathy and scrapie. J Comp Pathol 113:241–251CrossRefGoogle Scholar
  107. 107.
    Windl O, Buchholz M, Neubauer A, Schulz-Schaeffer W, Groschup M, Walter S, Arendt S, Neumann M, Voss AK, Kretzschmar HA (2005) Breaking an absolute species barrier: transgenic mice expressing the mink PrP gene are susceptible to transmissible mink encephalopathy. J Virol 79:14971–14975CrossRefGoogle Scholar
  108. 108.
    Mastrianni JA, Nixon R, Layzer R, Telling GC, Han D, DeArmond SJ, Prusiner SB (1999) Prion protein conformation in a patient with sporadic fatal insomnia. N Engl J Med 340:1630–1638CrossRefGoogle Scholar
  109. 109.
    Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A, Smith PG (1996) A new variant of Creutzfeldt–Jakob disease in the UK. Lancet 347:921–925CrossRefGoogle Scholar
  110. 110.
    Bruce ME, Will RG, Ironside JW, McConnell I, Drummond D, Suttie A, McCardle L, Chree A, Hope J, Birkett C, Cousens S, Fraser H, Bostock CJ (1997) Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389:498–501CrossRefGoogle Scholar
  111. 111.
    Collinge J, Sidle KC, Meads J, Ironside J, Hill AF (1996) Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383:685–690CrossRefGoogle Scholar
  112. 112.
    Hill AF, Desbruslais M, Joiner S, Sidle KCL, Gowland I, Collinge J, Doey LJ, Lantos P (1997) The same prion strain causes vCJD and BSE. Nature 389:448–450CrossRefGoogle Scholar
  113. 113.
    Collinge J, Whitfield J, McKintosh E, Beck J, Mead S, Thomas DJ, Alpers MP (2006) Kuru in the 21st century–an acquired human prion disease with very long incubation periods. Lancet 367:2068–2074CrossRefGoogle Scholar
  114. 114.
    Llewelyn CA, Hewitt PE, Knight RS, Amar K, Cousens S, Mackenzie J, Will RG (2004) Possible transmission of variant Creutzfeldt–Jakob disease by blood transfusion. Lancet 363:417–421CrossRefGoogle Scholar
  115. 115.
    Wroe SJ, Pal S, Siddique D, Hyare H, Macfarlane R, Joiner S, Linehan JM, Brandner S, Wadsworth JD, Hewitt P, Collinge J (2006) Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt–Jakob disease associated with blood transfusion: a case report. Lancet 368:2061–2067CrossRefGoogle Scholar
  116. 116.
    Brown P, Gibbs CJ Jr, Rodgers-Johnson P, Asher DM, Sulima MP, Bacote A, Goldfarb LG, Gajdusek DC (1994) Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol 35:513–529CrossRefGoogle Scholar
  117. 117.
    Gibbs CJ Jr, Gajdusek DC, Amyx H (1979) Strain variation in the viruses of Creutzfeldt–Jakob disease and kuru. In: Prusiner SB, Hadlow WJ (eds) Slow transmissible diseases of the nervous system, vol 2. Academic, New York, pp 87–110Google Scholar
  118. 118.
    Manuelidis E, Gorgacz EJ, Manuelidis L (1978) Interspecies transmission of Creutzfeldt–Jakob disease to Syrian hamsters with reference to clinical syndromes and strains of agent. Proc Natl Acad Sci USA 75:3422–3436CrossRefGoogle Scholar
  119. 119.
    Manuelidis E, Kim J, Angelo J, Manuelidis L (1976) Serial propagation of Creutzfeldt–Jakob disease in guinea pigs. Proc Natl Acad Sci USA 73:223–227CrossRefGoogle Scholar
  120. 120.
    Tateishi J, Kitamoto T (1995) Inherited prion diseases and transmission to rodents. Brain Pathol 5:53–59CrossRefGoogle Scholar
  121. 121.
    Tateishi J, Sato Y, Ohta M (1983) Creutzfeldt–Jakob disease in humans and laboratory animals. In: Zimmerman HM (ed) Progress in neuropathology, vol 5. Raven Press, New York, pp 195–221Google Scholar
  122. 122.
    Scott MR, Köhler R, Foster D, Prusiner SB (1992) Chimeric prion protein expression in cultured cells and transgenic mice. Protein Sci 1:986–997CrossRefGoogle Scholar
  123. 123.
    Telling GC, Parchi P, DeArmond SJ, Cortelli P, Montagna P, Gabizon R, Mastrianni J, Lugaresi E, Gambetti P, Prusiner SB (1996) Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity. Science 274:2079–2082CrossRefGoogle Scholar
  124. 124.
    Bessen RA, Marsh RF (1994) Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy. J Virol 68:7859–7868Google Scholar
  125. 125.
    Hill AF, Joiner S, Wadsworth JD, Sidle KC, Bell JE, Budka H, Ironside JW, Collinge J (2003) Molecular classification of sporadic Creutzfeldt–Jakob disease. Brain 126:1333–1346CrossRefGoogle Scholar
  126. 126.
    Parchi P, Castellani R, Capellari S, Ghetti B, Young K, Chen SG, Farlow M, Dickson DW, Sima AAF, Trojanowski JQ, Petersen RB, Gambetti P (1996) Molecular basis of phenotypic variability in sporadic Creutzfeldt–Jakob disease. Ann Neurol 39:767–778CrossRefGoogle Scholar
  127. 127.
    Polymenidou M, Stoeck K, Glatzel M, Vey M, Bellon A, Aguzzi A (2005) Coexistence of multiple PrPSc types in individuals with Creutzfeldt–Jakob disease. Lancet Neurol 4:805–814CrossRefGoogle Scholar
  128. 128.
    Giles K, Glidden DV, Patel S, Korth C, Groth D, Lemus A, DeArmond SJ, Prusiner SB (2010) Human prion strain selection in transgenic mice. Ann Neurol 68:151–161CrossRefGoogle Scholar
  129. 129.
    Bishop MT, Will RG, Manson JC (2010) Defining sporadic Creutzfeldt–Jakob disease strains and their transmission properties. Proc Natl Acad Sci USA 107:12005–12010CrossRefGoogle Scholar
  130. 130.
    Nonno R, Di Bari MA, Cardone F, Vaccari G, Fazzi P, Dell’Omo G, Cartoni C, Ingrosso L, Boyle A, Galeno R, Sbriccoli M, Lipp HP, Bruce M, Pocchiari M, Agrimi U (2006) Efficient transmission and characterization of Creutzfeldt–Jakob disease strains in bank voles. PLoS Pathog 2:e12CrossRefGoogle Scholar
  131. 131.
    Mead S, Poulter M, Uphill J, Beck J, Whitfield J, Webb TE, Campbell T, Adamson G, Deriziotis P, Tabrizi SJ, Hummerich H, Verzilli C, Alpers MP, Whittaker JC, Collinge J (2009) Genetic risk factors for variant Creutzfeldt–Jakob disease: a genome-wide association study. Lancet Neurol 8:57–66CrossRefGoogle Scholar
  132. 132.
    Collinge J, Palmer MS, Sidle KC, Hill AF, Gowland I, Meads J, Asante E, Bradley R, Doey LJ, Lantos PL (1995) Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature 378:779–783CrossRefGoogle Scholar
  133. 133.
    Plinston C, Hart P, Chong A, Hunter N, Foster J, Piccardo P, Manson JC, Barron RM (2011) Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy infection following passage in sheep. J Virol 85:1174–1181CrossRefGoogle Scholar
  134. 134.
    Peretz D, Williamson RA, Legname G, Matsunaga Y, Vergara J, Burton DR, DeArmond SJ, Prusiner SB, Scott MR (2002) A change in the conformation of prions accompanies the emergence of a new prion strain. Neuron 34:921–932CrossRefGoogle Scholar
  135. 135.
    Scott MR, Peretz D, Nguyen HO, Dearmond SJ, Prusiner SB (2005) Transmission barriers for bovine, ovine, and human prions in transgenic mice. J Virol 79:5259–5271CrossRefGoogle Scholar
  136. 136.
    Collinge J (1999) Variant Creutzfeldt–Jakob disease. Lancet 354:317–323CrossRefGoogle Scholar
  137. 137.
    Collinge J, Clarke AR (2007) A general model of prion strains and their pathogenicity. Science 318:930–936CrossRefGoogle Scholar
  138. 138.
    Li J, Browning S, Mahal SP, Oelschlegel AM, Weissmann C (2010) Darwinian evolution of prions in cell culture. Science 327:869–872CrossRefGoogle Scholar
  139. 139.
    Angers RC, Browning SR, Seward TS, Sigurdson CJ, Miller MW, Hoover EA, Telling GC (2006) Prions in skeletal muscles of deer with chronic wasting disease. Science 311:1117CrossRefGoogle Scholar
  140. 140.
    Race B, Meade-White K, Race R, Chesebro B (2009) Prion infectivity in fat of deer with chronic wasting disease. J Virol 83:9608–9610CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin-Heidelberg 2011

Authors and Affiliations

  1. 1.Sanders Brown Center on AgingUniversity of Kentucky Medical CenterLexingtonUSA
  2. 2.Department of Microbiology, Immunology and Molecular GeneticsUniversity of Kentucky Medical CenterLexingtonUSA
  3. 3.Department of NeurologyUniversity of Kentucky Medical CenterLexingtonUSA

Personalised recommendations