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Insights into Mechanisms of Transmission and Pathogenesis from Transgenic Mouse Models of Prion Diseases

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Prions

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1658))

Abstract

Prions represent a new paradigm of protein-mediated information transfer. In the case of mammals, prions are the cause of fatal, transmissible neurodegenerative diseases, sometimes referred to as transmissible spongiform encephalopathies (TSEs), which frequently occur as epidemics. An increasing body of evidence indicates that the canonical mechanism of conformational corruption of cellular prion protein (PrPC) by the pathogenic isoform (PrPSc) that is the basis of prion formation in TSEs is common to a spectrum of proteins associated with various additional human neurodegenerative disorders, including the more common Alzheimer’s and Parkinson’s diseases. The peerless infectious properties of TSE prions, and the unparalleled tools for their study, therefore enable elucidation of mechanisms of template-mediated conformational propagation that are generally applicable to these related disease states. Many unresolved issues remain including the exact molecular nature of the prion, the detailed cellular and molecular mechanisms of prion propagation, and the means by which prion diseases can be both genetic and infectious. In addition, we know little about the mechanism by which neurons degenerate during prion diseases. Tied to this, the physiological role of the normal form of the prion protein remains unclear and it is uncertain whether or not loss of this function contributes to prion pathogenesis. The factors governing the transmission of prions between species remain unclear, in particular the means by which prion strains and PrP primary structure interact to affect interspecies prion transmission. Despite all these unknowns, advances in our understanding of prions have occurred because of their transmissibility to experimental animals, and the development of transgenic (Tg) mouse models has done much to further our understanding about various aspects of prion biology. In this review, we will focus on advances in our understanding of prion biology that occurred in the past 8 years since our last review of this topic.

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References

  1. Prusiner SB (1998) Prions (Les Prix Nobel Lecture). In: Frängsmyr T (ed) Les Prix Nobel. Almqvist & Wiksell International, Stockholm, Sweden, pp 268–323

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Scott M, Groth D, Foster D et al (1993) Propagation of prions with artificial properties in transgenic mice expressing chimeric PrP genes. Cell 73:979–988

    Article  CAS  PubMed  Google Scholar 

  4. Kocisko DA, Come JH, Priola SA et al (1994) Cell-free formation of protease-resistant prion protein. Nature 370:471–474

    Article  CAS  PubMed  Google Scholar 

  5. Vidal E, Fernandez-Borges N, Pintado B et al (2015) Transgenic mouse bioassay: evidence that rabbits are susceptible to a variety of prion isolates. PLoS Pathog 11:e1004977

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Chianini F, Fernandez-Borges N, Vidal E et al (2012) Rabbits are not resistant to prion infection. Proc Natl Acad Sci U S A 109:5080–5085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Westaway D, Goodman PA, Mirenda CA et al (1987) Distinct prion proteins in short and long scrapie incubation period mice. Cell 51:651–662

    Article  CAS  PubMed  Google Scholar 

  8. Hunter N, Goldmann W, Marshall E et al (2000) Sheep and goats: natural and experimental TSEs and factors influencing incidence of disease. Arch Virol Suppl 16:181–188

    Google Scholar 

  9. Baker HF, Poulter M, Crow TJ et al (1991) Amino acid polymorphism in human prion protein and age at death in inherited prion disease. Lancet 337:1286

    Article  CAS  PubMed  Google Scholar 

  10. Collinge J, Palmer MS, Dryden AJ (1991) Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. Lancet 337:1441–1442

    Article  CAS  PubMed  Google Scholar 

  11. Palmer MS, Dryden AJ, Hughes JT et al (1991) Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease. Nature 352:340–342

    Article  CAS  PubMed  Google Scholar 

  12. Nonno R, Di Bari MA, Cardone F et al (2006) Efficient transmission and characterization of Creutzfeldt-Jakob disease strains in bank voles. PLoS Pathog 2:e12

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Telling GC, Parchi P, Dearmond SJ et al (1996) Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity. Science 274:2079–2082

    Article  CAS  PubMed  Google Scholar 

  14. Bessen RA, Marsh RF (1994) Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy. J Virol 68:7859–7868

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Safar J, Wille H, Itri V et al (1998) Eight prion strains have PrPSc molecules with different conformations. Nat Med 4:1157–1165

    Article  CAS  PubMed  Google Scholar 

  16. Peretz D, Williamson RA, Legname G et al (2002) A change in the conformation of prions accompanies the emergence of a new prion strain. Neuron 34:921–932

    Article  CAS  PubMed  Google Scholar 

  17. Collinge J, Sidle KCL, Meads J et al (1996) Molecular analysis of prion strain variation and the aetiology of “new variant” CJD. Nature 383:685–690

    Article  CAS  PubMed  Google Scholar 

  18. Hill AF, Desbruslais M, Joiner S et al (1997) The same prion strain causes vCJD and BSE. Nature 389:448–450

    Article  CAS  PubMed  Google Scholar 

  19. Scott MR, Peretz D, Nguyen HO et al (2005) Transmission barriers for bovine, ovine, and human prions in transgenic mice. J Virol 79:5259–5271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Asante EA, Linehan JM, Desbruslais M et al (2002) BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J 21:6358–6366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Korth C, Kaneko K, Groth D et al (2003) Abbreviated incubation times for human prions in mice expressing a chimeric mouse-human prion protein transgene. Proc Natl Acad Sci U S A 100:4784–4789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Scott MR, Will R, Ironside J et al (1999) Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc Natl Acad Sci U S A 96(26):15137–15142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  24. Collinge J, Clarke AR (2007) A general model of prion strains and their pathogenicity. Science 318:930–936

    Article  CAS  PubMed  Google Scholar 

  25. Haldiman T, Kim C, Cohen Y et al (2013) Co-existence of distinct prion types enables conformational evolution of human PrPSc by competitive selection. J Biol Chem 288:29846–29861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Collinge J (1999) Variant Creutzfeldt-Jakob disease. Lancet 354:317–323

    Article  CAS  PubMed  Google Scholar 

  27. Eigen M (1996) On the nature of virus quasispecies. Trends Microbiol 4:216–218

    Article  CAS  PubMed  Google Scholar 

  28. Li J, Browning S, Mahal SP et al (2010) Darwinian evolution of prions in cell culture. Science 327:869–872

    Article  CAS  PubMed  Google Scholar 

  29. Angers RC, Kang HE, Napier D et al (2010) Prion strain mutation determined by prion protein conformational compatibility and primary structure. Science 328:1154–1158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bian J, Kang HE, Telling GC (2014) Quinacrine promotes replication and conformational mutation of chronic wasting disease prions. Proc Natl Acad Sci U S A 111:6028–6033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Makarava N, Baskakov IV (2008) The same primary structure of the prion protein yields two distinct self-propagating states. J Biol Chem 283:15988–15996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Rezaei H, Choiset Y, Eghiaian F et al (2002) Amyloidogenic unfolding intermediates differentiate sheep prion protein variants. J Mol Biol 322:799–814

    Article  CAS  PubMed  Google Scholar 

  33. Beringue V, Herzog L, Jaumain E et al (2012) Facilitated cross-species transmission of prions in extraneural tissue. Science 335:472–475

    Article  CAS  PubMed  Google Scholar 

  34. Rogers M, Yehiely F, Scott M et al (1993) Conversion of truncated and elongated prion proteins into the scrapie isoform in cultured cells. Proc Natl Acad Sci U S A 90:3182–3186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Chesebro B, Trifilo M, Race R et al (2005) Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science 308:1435–1439

    Article  CAS  PubMed  Google Scholar 

  36. Telling GC, Scott M, Hsiao KK et al (1994) Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein. Proc Natl Acad Sci U S A 91:9936–9940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Telling GC, Scott M, Mastrianni J et al (1995) Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell 83:79–90

    Article  CAS  PubMed  Google Scholar 

  38. Perrier V, Kaneko K, Safar J et al (2002) Dominant-negative inhibition of prion replication in transgenic mice. Proc Natl Acad Sci U S A 99:13079–13084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Geoghegan JC, Miller MB, Kwak AH et al (2009) Trans-dominant inhibition of prion propagation in vitro is not mediated by an accessory cofactor. PLoS Pathog 5:e1000535

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Christen B, Hornemann S, Damberger FF et al (2009) Prion protein NMR structure from tammar wallaby (Macropus eugenii) shows that the beta2-alpha2 loop is modulated by long-range sequence effects. J Mol Biol 389:833–845

    Article  CAS  PubMed  Google Scholar 

  41. Perez DR, Damberger FF, Wuthrich K (2010) Horse prion protein NMR structure and comparisons with related variants of the mouse prion protein. J Mol Biol 400:121–128

    Article  CAS  PubMed  Google Scholar 

  42. Telling GC, Haga T, Torchia M et al (1996) Interactions between wild-type and mutant prion proteins modulate neurodegeneration in transgenic mice. Genes Dev 10:1736–1750

    Article  CAS  PubMed  Google Scholar 

  43. Chiesa R, Drisaldi B, Quaglio E et al (2000) Accumulation of protease-resistant prion protein (PrP) and apoptosis of cerebellar granule cells in transgenic mice expressing a PrP insertional mutation. Proc Natl Acad Sci U S A 97:5574–5579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bian J, Nazor KE, Angers R et al (2006) GFP-tagged PrP supports compromised prion replication in transgenic mice. Biochem Biophys Res Commun 340:894–900

    Article  CAS  PubMed  Google Scholar 

  45. Barmada SJ, Harris DA (2005) Visualization of prion infection in transgenic mice expressing green fluorescent protein-tagged prion protein. J Neurosci 25:5824–5832

    Article  CAS  PubMed  Google Scholar 

  46. Shmerling D, Hegyi I, Fischer M et al (1998) Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Cell 93:203–214

    Article  CAS  PubMed  Google Scholar 

  47. Baumann F, Tolnay M, Brabeck C et al (2007) Lethal recessive myelin toxicity of prion protein lacking its central domain. EMBO J 26:538–547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Li A, Christensen HM, Stewart LR et al (2007) Neonatal lethality in transgenic mice expressing prion protein with a deletion of residues 105–125. EMBO J 26:548–558

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Scott M, Foster D, Mirenda C et al (1989) Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques. Cell 59:847–857

    Article  CAS  PubMed  Google Scholar 

  50. Angers R, Christiansen J, Nalls AV et al (2014) Structural effects of PrP polymorphisms on intra- and interspecies prion transmission. Proc Natl Acad Sci U S A 111:11169–11174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Telling GC (2010) Nucleic acid-free mutation of prion strains. Prion 4:252–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Büeler H, Fischer M, Lang Y et al (1992) Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356:577–582

    Article  PubMed  Google Scholar 

  53. Gombojav A, Shimauchi I, Horiuchi M et al (2003) Susceptibility of transgenic mice expressing chimeric sheep, bovine and human PrP genes to sheep scrapie. J Vet Med Sci 65:341–347

    Article  CAS  PubMed  Google Scholar 

  54. Kupfer L, Eiden M, Buschmann A et al (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 1772:704–713

    Article  CAS  PubMed  Google Scholar 

  55. Scott MR, Safar J, Telling G et al (1997) Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice. Proc Natl Acad Sci U S A 94:14279–14284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bishop MT, Hart P, Aitchison L et al (2006) Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 5:393–398

    Article  CAS  PubMed  Google Scholar 

  57. Hadlow WJ (1959) Scrapie and kuru. Lancet 2:289–290

    Article  Google Scholar 

  58. Gajdusek DC, Gibbs CJ Jr, Alpers M (1966) Experimental transmission of a kuru-like syndrome to chimpanzees. Nature 209:794–796

    Article  CAS  PubMed  Google Scholar 

  59. Gibbs CJ Jr, Gajdusek DC, Asher DM et al (1968) Creutzfeldt-Jakob disease (spongiform encephalopathy): transmission to the chimpanzee. Science 161:388–389

    Article  PubMed  Google Scholar 

  60. Brown P, Gibbs CJ Jr, Rodgers-Johnson P et al (1994) Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol 35:513–529

    Article  CAS  PubMed  Google Scholar 

  61. 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 87–110

    Google Scholar 

  62. 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 195–221

    Google Scholar 

  63. Tateishi J, Kitamoto T (1995) Inherited prion diseases and transmission to rodents. Brain Pathol 5:53–59

    Article  CAS  PubMed  Google Scholar 

  64. Manuelidis E, Kim J, Angelo J et al (1976) Serial propagation of Creutzfeldt-Jakob disease in guinea pigs. Proc Natl Acad Sci U S A 73:223–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. 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 U S A 75:3422–3436

    Article  Google Scholar 

  66. Scott MR, Köhler R, Foster D et al (1992) Chimeric prion protein expression in cultured cells and transgenic mice. Protein Sci 1:986–997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kong Q, Zheng M, Casalone C et al (2008) Evaluation of the human transmission risk of an atypical bovine spongiform encephalopathy prion strain. J Virol 82:3697–3701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Beringue V, Herzog L, Reine F et al (2008) Transmission of atypical bovine prions to mice transgenic for human prion protein. Emerg Infect Dis 14:1898–1901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Bishop MT, Will RG, Manson JC (2010) Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties. Proc Natl Acad Sci U S A 107:12005–12010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hill AF, Joiner S, Wadsworth JD et al (2003) Molecular classification of sporadic Creutzfeldt-Jakob disease. Brain 126:1333–1346

    Article  PubMed  Google Scholar 

  71. Parchi P, Castellani R, Capellari S et al (1996) Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease. Ann Neurol 39:767–778

    Article  CAS  PubMed  Google Scholar 

  72. Polymenidou M, Stoeck K, Glatzel M et al (2005) Coexistence of multiple PrPSc types in individuals with Creutzfeldt-Jakob disease. Lancet Neurol 4:805–814

    Article  CAS  PubMed  Google Scholar 

  73. Mastrianni JA, Capellari S, Telling GC et al (2001) Inherited prion disease caused by the V210I mutation: transmission to transgenic mice. Neurology 57:2198–2205

    Article  CAS  PubMed  Google Scholar 

  74. Mastrianni J, Nixon F, Layzer R et al (1997) Fatal sporadic insomnia: fatal familial insomnia phenotype without a mutation of the prion protein gene. Neurology 48(Suppl):A296

    Google Scholar 

  75. Notari S, Xiao X, Espinosa JC et al (2014) Transmission characteristics of variably protease-sensitive prionopathy. Emerg Infect Dis 20:2006–2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Diack AB, Ritchie DL, Peden AH et al (2014) Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties. Emerg Infect Dis 20:1969–1979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Giles K, Glidden DV, Patel S et al (2010) Human prion strain selection in transgenic mice. Ann Neurol 68:151–161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Will RG, Ironside JW, Zeidler M et al (1996) A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347:921–925

    Article  CAS  PubMed  Google Scholar 

  79. Collinge J, Palmer MS, Sidle KC et al (1995) Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature 378:779–783

    Article  CAS  PubMed  Google Scholar 

  80. Mead S, Poulter M, Uphill J et al (2009) Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study. Lancet Neurol 8:57–66

    Article  PubMed  PubMed Central  Google Scholar 

  81. Plinston C, Hart P, Chong A et al (2011) Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy infection following passage in sheep. J Virol 85:1174–1181

    Article  CAS  PubMed  Google Scholar 

  82. Plinston C, Hart P, Hunter N et al (2014) Increased susceptibility of transgenic mice expressing human PrP to experimental sheep bovine spongiform encephalopathy is not due to increased agent titre in sheep brain tissue. J Gen Virol 95:1855–1859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Asante EA, Linehan JM, Gowland I et al (2006) Dissociation of pathological and molecular phenotype of variant Creutzfeldt-Jakob disease in transgenic human prion protein 129 heterozygous mice. Proc Natl Acad Sci U S A 103:10759–10764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Mead S, Whitfield J, Poulter M et al (2009) A novel protective prion protein variant that colocalizes with kuru exposure. N Engl J Med 361:2056–2065

    Article  CAS  PubMed  Google Scholar 

  85. Asante EA, Smidak M, Grimshaw A et al (2015) A naturally occurring variant of the human prion protein completely prevents prion disease. Nature 522:478–481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hsiao K, Baker HF, Crow TJ et al (1989) Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome. Nature 338:342–345

    Article  CAS  PubMed  Google Scholar 

  87. Manson JC, Jamieson E, Baybutt H et al (1999) A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy. EMBO J 18:6855–6864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hsiao KK, Groth D, Scott M et al (1994) Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein. Proc Natl Acad Sci U S A 91:9126–9130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Kaneko K, Ball HL, Wille H, Zhang H, Groth D, Torchia M, Tremblay P, Safar J, Prusiner SB, Dearmond SJ, Baldwin MA, Cohen FE (2000) A synthetic peptide initiates Gerstmann-Straussler-Scheinker (GSS) disease in transgenic mice. J Mol Biol 295:997–1007

    Article  CAS  PubMed  Google Scholar 

  90. Tremblay P, Ball HL, Kaneko K et al (2004) Mutant PrPSc conformers induced by a synthetic peptide and several prion strains. J Virol 78:2088–2099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Cohen FE, Pan K-M, Huang Z et al (1994) Structural clues to prion replication. Science 264:530–531

    Article  CAS  PubMed  Google Scholar 

  92. Tzaban S, Friedlander G, Schonberger O et al (2002) Protease-sensitive scrapie prion protein in aggregates of heterogeneous sizes. Biochemistry 41:12868–12875

    Article  CAS  PubMed  Google Scholar 

  93. Korth C, Stierli B, Streit P et al (1997) Prion (PrPSc)-specific epitope defined by a monoclonal antibody. Nature 389:74–77

    Article  Google Scholar 

  94. Nazor KE, Kuhn F, Seward T et al (2005) Immunodetection of disease-associated mutant PrP, which accelerates disease in GSS transgenic mice. EMBO J 24:2472–2480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Uptain SM, Lindquist S (2002) Prions as protein-based genetic elements. Annu Rev Microbiol 56:703–741

    Article  CAS  PubMed  Google Scholar 

  96. Piccardo P, King D, Telling G et al (2013) Dissociation of prion protein amyloid seeding from transmission of a spongiform encephalopathy. J Virol 87:12349–12356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Legname G, Baskakov IV, Nguyen HO et al (2004) Synthetic mammalian prions. Science 305:673–676

    Article  CAS  PubMed  Google Scholar 

  98. Asante EA, Grimshaw A, Smidak M et al (2015) Transmission properties of human PrP 102L prions challenge the relevance of mouse models of GSS. PLoS Pathog 11:e1004953

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Friedman-Levi Y, Meiner Z, Canello T et al (2011) Fatal prion disease in a mouse model of genetic E200K Creutzfeldt-Jakob disease. PLoS Pathog 7:e1002350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Chiesa R, Piccardo P, Ghetti B et al (1998) Neurological illness in transgenic mice expressing a prion protein with an insertional mutation. Neuron 21:1339–1351

    Article  CAS  PubMed  Google Scholar 

  101. Chiesa R, Piccardo P, Quaglio E et al (2003) Molecular distinction between pathogenic and infectious properties of the prion protein. J Virol 77:7611–7622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Dossena S, Imeri L, Mangieri M et al (2008) Mutant prion protein expression causes motor and memory deficits and abnormal sleep patterns in a transgenic mouse model. Neuron 60:598–609

    Article  CAS  PubMed  Google Scholar 

  103. Bouybayoune I, Mantovani S, Del Gallo F et al (2015) Transgenic fatal familial insomnia mice indicate prion infectivity-independent mechanisms of pathogenesis and phenotypic expression of disease. PLoS Pathog 11:e1004796

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Jackson WS, Borkowski AW, Faas H et al (2009) Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice. Neuron 63:438–450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Jackson WS, Borkowski AW, Watson NE et al (2013) Profoundly different prion diseases in knock-in mice carrying single PrP codon substitutions associated with human diseases. Proc Natl Acad Sci U S A 110:14759–14764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Hsiao KK, Cass C, Schellenberg GD et al (1991) A prion protein variant in a family with the telencephalic form of Gerstmann-Sträussler-Scheinker syndrome. Neurology 41:681–684

    Article  CAS  PubMed  Google Scholar 

  107. Hegde RS, Mastrianni JA, Scott MR et al (1998) A transmembrane form of the prion protein in neurodegenerative disease. Science 279:827–834

    Article  CAS  PubMed  Google Scholar 

  108. Yang W, Cook J, Rassbach B et al (2009) A new transgenic mouse model of Gerstmann-Straussler-Scheinker syndrome caused by the A117V mutation of PRNP. J Neurosci 29:10072–10080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Asante EA, Linehan JM, Smidak M et al (2013) Inherited prion disease A117V is not simply a proteinopathy but produces prions transmissible to transgenic mice expressing homologous prion protein. PLoS Pathog 9:e1003643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Buschmann A, Pfaff E, Reifenberg K et al (2000) Detection of cattle-derived BSE prions using transgenic mice overexpressing bovine PrP(C). Arch Virol Suppl 16:75–86

    Google Scholar 

  111. Castilla J, Gutierrez Adan A, Brun A et al (2003) Early detection of PrPres in BSE-infected bovine PrP transgenic mice. Arch Virol 148:677–691

    Article  CAS  PubMed  Google Scholar 

  112. Jacobs JG, Langeveld JP, Biacabe AG et al (2007) Molecular discrimination of atypical bovine spongiform encephalopathy strains from a geographical region spanning a wide area in Europe. J Clin Microbiol 45:1821–1829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Casalone C, Zanusso G, Acutis P et al (2004) Identification of a second bovine amyloidotic spongiform encephalopathy: molecular similarities with sporadic Creutzfeldt-Jakob disease. Proc Natl Acad Sci U S A 101:3065–3070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Richt JA, Hall SM (2008) BSE case associated with prion protein gene mutation. PLoS Pathog 4:e1000156

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. 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 192:934–942

    Article  PubMed  Google Scholar 

  116. Beringue V, Bencsik A, Le Dur A et al (2006) Isolation from cattle of a prion strain distinct from that causing bovine spongiform encephalopathy. PLoS Pathog 2:e112

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Beringue V, Andreoletti O, Le Dur A et al (2007) A bovine prion acquires an epidemic bovine spongiform encephalopathy strain-like phenotype on interspecies transmission. J Neurosci 27:6965–6971

    Article  CAS  PubMed  Google Scholar 

  118. Buschmann A, Gretzschel A, Biacabe AG et al (2006) Atypical BSE in Germany—proof of transmissibility and biochemical characterization. Vet Microbiol 117:103–116

    Article  CAS  PubMed  Google Scholar 

  119. Capobianco R, Casalone C, Suardi S et al (2007) Conversion of the BASE prion strain into the BSE strain: the origin of BSE? PLoS Pathog 3:e31

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Wadsworth JD, Asante EA, Desbruslais M et al (2004) Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science 306:1793–1796

    Article  CAS  PubMed  Google Scholar 

  121. Beringue V, Le Dur A, Tixador P et al (2008) Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD. PLoS One 3:e1419

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Espinosa JC, Herva ME, Andreoletti O et al (2009) Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie. Emerg Infect Dis 15:1214–1221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Westaway D, Dearmond SJ, Cayetano-Canlas J et al (1994) Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice overexpressing wild-type prion proteins. Cell 76:117–129

    Article  CAS  PubMed  Google Scholar 

  124. Rubenstein R, Bulgin MS, Chang B et al (2012) PrP(Sc) detection and infectivity in semen from scrapie-infected sheep. J Gen Virol 93:1375–1383

    Article  CAS  PubMed  Google Scholar 

  125. Crozet C, Flamant F, Bencsik A et al (2001) Efficient transmission of two different sheep scrapie isolates in transgenic mice expressing the ovine PrP gene. J Virol 75:5328–5334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Crozet C, Bencsik A, Flamant F et al (2001) Florid plaques in ovine PrP transgenic mice infected with an experimental ovine BSE. EMBO rep 2:952–956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Vilotte JL, 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Tamguney G, Miller MW, Giles K et al (2009) Transmission of scrapie and sheep-passaged bovine spongiform encephalopathy prions to transgenic mice expressing elk prion protein. J Gen Virol 90:1035–1047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Goldmann W, Hunter N, Smith G et al (1994) PrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie. J Gen Virol 75:989–995

    Article  CAS  PubMed  Google Scholar 

  130. Cordier C, Bencsik A, Philippe S et al (2006) Transmission and characterization of bovine spongiform encephalopathy sources in two ovine transgenic mouse lines (TgOvPrP4 and TgOvPrP59). J Gen Virol 87:3763–3771

    Article  CAS  PubMed  Google Scholar 

  131. Saijo E, Kang HE, Bian J et al (2013) Epigenetic dominance of prion conformers. PLoS Pathog 9:e1003692

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Foster JD, Dickinson AG (1988) The unusual properties of CH 1641, a sheep-passaged isolate of scrapie. Vet Rec 123:5–8

    Article  CAS  PubMed  Google Scholar 

  133. Baron T, Biacabe AG (2007) Molecular behaviors of “CH1641-like” sheep scrapie isolates in ovine transgenic mice (TgOvPrP4). J Virol 81:7230–7237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Kang HE, Weng CC, Saijo E et al (2012) Characterization of conformation-dependent prion protein epitopes. J Biol Chem 287(44):37219–37232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Bencsik A, Philippe S, Debeer S et al (2007) Scrapie strain transmission studies in ovine PrP transgenic mice reveal dissimilar susceptibility. Histochem Cell Biol 127:531–539

    Article  CAS  PubMed  Google Scholar 

  136. Baron T, Crozet C, Biacabe AG et al (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 78:6243–6251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Le Dur A, Beringue V, Andreoletti O et al (2005) A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes. Proc Natl Acad Sci U S A 102:16031–16036

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Simmons MM, Konold T, Simmons HA et al (2007) Experimental transmission of atypical scrapie to sheep. BMC Vet Res 3:20

    Article  PubMed  PubMed Central  Google Scholar 

  139. Wadsworth JD, Joiner S, Linehan JM et al (2013) Atypical scrapie prions from sheep and lack of disease in transgenic mice overexpressing human prion protein. Emerg Infect Dis 19:1731–1739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Cassard H, Torres JM, Lacroux C et al (2014) Evidence for zoonotic potential of ovine scrapie prions. Nat Commun 5:5821

    Article  CAS  PubMed  Google Scholar 

  141. Mathiason CK, Powers JG, Dahmes SJ et al (2006) Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 314:133–136

    Article  CAS  PubMed  Google Scholar 

  142. Browning SR, Mason GL, Seward T et al (2004) Transmission of prions from mule deer and elk with chronic wasting disease to transgenic mice expressing cervid PrP. J Virol 78:13345–13350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Bartz JC, Marsh RF, Mckenzie DI et al (1998) The host range of chronic wasting disease is altered on passage in ferrets. Virology 251:297–301

    Article  CAS  PubMed  Google Scholar 

  144. Angers RC, Browning SR, Seward TS et al (2006) Prions in skeletal muscles of deer with chronic wasting disease. Science 311:1117

    Article  CAS  PubMed  Google Scholar 

  145. Meade-White K, Race B, Trifilo M et al (2007) Resistance to chronic wasting disease in transgenic mice expressing a naturally occurring allelic variant of deer prion protein. J Virol 81:4533–4539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Lafauci G, Carp RI, Meeker HC et al (2006) Passage of chronic wasting disease prion into transgenic mice expressing Rocky Mountain elk (Cervus elaphus nelsoni) PrPC. J Gen Virol 87:3773–3780

    Article  CAS  PubMed  Google Scholar 

  147. Tamguney G, Giles K, Bouzamondo-Bernstein E et al (2006) Transmission of elk and deer prions to transgenic mice. J Virol 80:9104–9114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Kong Q, Huang S, Zou W et al (2005) Chronic wasting disease of elk: transmissibility to humans examined by transgenic mouse models. J Neurosci 25:7944–7949

    Article  CAS  PubMed  Google Scholar 

  149. Sigurdson CJ, Manco G, Schwarz P et al (2006) Strain fidelity of chronic wasting disease upon murine adaptation. J Virol 80:12303–12311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Raymond GJ, Raymond LD, Meade-White KD et al (2007) Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains. J Virol 81:4305–4314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Meyerett C, Michel B, Pulford B et al (2008) In vitro strain adaptation of CWD prions by serial protein misfolding cyclic amplification. Virology 382(2):267–276

    Article  CAS  PubMed  Google Scholar 

  152. Green KM, Castilla J, Seward TS et al (2008) Accelerated high fidelity prion amplification within and across prion species barriers. PLoS Pathog 4:e1000139

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. Kurt TD, Perrott MR, Wilusz CJ et al (2007) Efficient in vitro amplification of chronic wasting disease PrPRES. J Virol 81:9605–9608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Kurt TD, Telling GC, Zabel MD et al (2009) Trans-species amplification of PrP(CWD) and correlation with rigid loop 170N. Virology 387:235–243

    Article  CAS  PubMed  Google Scholar 

  155. Haley NJ, Seelig DM, Zabel MD et al (2009) Detection of CWD prions in urine and saliva of deer by transgenic mouse bioassay. PLoS One 4:e4848

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  156. Tamguney G, Miller MW, Wolfe LL et al (2009) Asymptomatic deer excrete infectious prions in faeces. Nature 461:529–532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Haley NJ, Mathiason CK, Zabel MD et al (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:e7990

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Pulford B, Spraker TR, Wyckoff AC et al (2012) Detection of PrPCWD in feces from naturally exposed Rocky Mountain elk (Cervus elaphus nelsoni) using protein misfolding cyclic amplification. J Wildl Dis 48:425–434

    Article  CAS  PubMed  Google Scholar 

  159. Henderson DM, Manca M, Haley NJ et al (2013) Rapid antemortem detection of CWD prions in deer saliva. PLoS One 8:e74377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Angers RC, Seward TS, Napier D et al (2009) Chronic wasting disease prions in elk antler velvet. Emerg Infect Dis 15:696–703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Race B, Meade-White K, Race R et al (2009) Prion infectivity in fat of deer with chronic wasting disease. J Virol 83:9608–9610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Johnson C, Johnson J, Clayton M et al (2003) Prion protein gene heterogeneity in free-ranging white-tailed deer within the chronic wasting disease affected region of Wisconsin. J Wildl Dis 39:576–581

    Article  CAS  PubMed  Google Scholar 

  163. Raymond GJ, Bossers A, Raymond LD et al (2000) Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease. EMBO J 19:4425–4430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Heaton MP, Leymaster KA, Freking BA et al (2003) Prion gene sequence variation within diverse groups of U.S. sheep, beef cattle, and deer. Mamm Genome 14:765–777

    Article  CAS  PubMed  Google Scholar 

  165. O'rourke KI, Spraker TR, Hamburg LK et al (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 85:1339–1346

    Article  PubMed  CAS  Google Scholar 

  166. Schatzl HM, Wopfner F, Gilch S et al (1997) Is codon 129 of prion protein polymorphic in human beings but not in animals? Lancet 349:1603–1604

    Article  CAS  PubMed  Google Scholar 

  167. O’rourke KI, Baszler TV, Miller JM et al (1998) Monoclonal antibody F89/160.1.5 defines a conserved epitope on the ruminant prion protein. J Clin Microbiol 36:1750–1755

    PubMed  PubMed Central  Google Scholar 

  168. O'rourke KI, Besser TE, Miller MW et al (1999) PrP genotypes of captive and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease. J Gen Virol 80(Pt 10):2765–2769

    Article  PubMed  Google Scholar 

  169. Hamir AN, Gidlewski T, Spraker TR et al (2006) Preliminary observations of genetic susceptibility of elk (Cervus elaphus nelsoni) to chronic wasting disease by experimental oral inoculation. J Vet Diagn Investig 18:110–114

    Article  Google Scholar 

  170. O’rourke KI, Spraker TR, Zhuang D et al (2007) Elk with a long incubation prion disease phenotype have a unique PrPd profile. Neuroreport 18:1935–1938

    Article  PubMed  CAS  Google Scholar 

  171. Green KM, Browning SR, Seward TS et al (2008) The elk PRNP codon 132 polymorphism controls cervid and scrapie prion propagation. J Gen Virol 89:598–608

    Article  CAS  PubMed  Google Scholar 

  172. Race B, Meade-White K, Miller MW et al (2011) In vivo comparison of chronic wasting disease infectivity from deer with variation at prion protein residue 96. J Virol 85:9235–9238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Keane DP, Barr DJ, Bochsler PN et al (2008) Chronic wasting disease in a Wisconsin white-tailed deer farm. J Vet Diagn Investig 20:698–703

    Article  Google Scholar 

  174. Duque Velasquez C, Kim C, Herbst A et al (2015) Deer prion proteins modulate the emergence and adaptation of chronic wasting disease strains. J Virol 89:12362–12373

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  175. Gossert AD, Bonjour S, Lysek DA et al (2005) Prion protein NMR structures of elk and of mouse/elk hybrids. Proc Natl Acad Sci U S A 102:646–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Sigurdson CJ, Nilsson KP, Hornemann S et al (2009) De novo generation of a transmissible spongiform encephalopathy by mouse transgenesis. Proc Natl Acad Sci U S A 106:304–309

    Article  CAS  PubMed  Google Scholar 

  177. Kurt TD, Bett C, Fernandez-Borges N et al (2014) Prion transmission prevented by modifying the beta2-alpha2 loop structure of host PrPC. J Neurosci 34:1022–1027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Sigurdson CJ, Nilsson KP, Hornemann S et al (2010) A molecular switch controls interspecies prion disease transmission in mice. J Clin Invest 120:2590–2599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Kurt TD, Jiang L, Fernandez-Borges N et al (2015) Human prion protein sequence elements impede cross-species chronic wasting disease transmission. J Clin Invest 125:1485–1496

    Article  PubMed  PubMed Central  Google Scholar 

  180. Khan MQ, Sweeting B, Mulligan VK et al (2010) Prion disease susceptibility is affected by beta-structure folding propensity and local side-chain interactions in PrP. Proc Natl Acad Sci U S A 107:19808–19813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Jewell JE, Conner MM, Wolfe LL et al (2005) Low frequency of PrP genotype 225SF among free-ranging mule deer (Odocoileus hemionus) with chronic wasting disease. J Gen Virol 86:2127–2134

    Article  CAS  PubMed  Google Scholar 

  182. Wolfe LL, Fox KA, Miller MW (2014) “Atypical” chronic wasting disease in PRNP genotype 225FF mule deer. J Wildl Dis 50:660–665

    Article  PubMed  Google Scholar 

  183. Johnson C, Johnson J, Vanderloo JP et al (2006) Prion protein polymorphisms in white-tailed deer influence susceptibility to chronic wasting disease. J Gen Virol 87:2109–2114

    Article  CAS  PubMed  Google Scholar 

  184. Bessen RA, Robinson CJ, Seelig DM et al (2011) Transmission of chronic wasting disease identifies a prion strain causing cachexia and heart infection in hamsters. PLoS One 6:e28026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Crowell J, Hughson A, Caughey B et al (2015) Host determinants of prion strain diversity independent of prion protein genotype. J Virol 89:10427–10441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Bruce ME, Will RG, Ironside JW et al (1997) Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389:498–501

    Article  CAS  PubMed  Google Scholar 

  187. Belay ED, Maddox RA, Williams ES et al (2004) Chronic wasting disease and potential transmission to humans. Emerg Infect Dis 10:977–984

    Article  PubMed  PubMed Central  Google Scholar 

  188. Mawhinney S, Pape WJ, Forster JE et al (2006) Human prion disease and relative risk associated with chronic wasting disease. Emerg Infect Dis 12:1527–1535

    Article  PubMed  Google Scholar 

  189. Barria MA, Telling GC, Gambetti P et al (2011) Generation of a new form of human PrP(Sc) in vitro by interspecies transmission from cervid prions. J Biol Chem 286:7490–7495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Sandberg M, Al-Doujaily H, Sigurdson C et al (2010) Chronic wasting disease prions are not transmissible to transgenic mice over-expressing human prion protein. J Gen Virol 91(Pt 10):2651–2657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Marsh RF, Kincaid AE, Bessen RA et al (2005) Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus). J Virol 79:13794–13796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Race B, Meade-White KD, Miller MW et al (2009) Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis 15:1366–1376

    Article  PubMed  PubMed Central  Google Scholar 

  193. Davenport KA, Henderson DM, Bian J et al (2015) Insights into chronic wasting disease and bovine spongiform encephalopathy species barriers by use of real-time conversion. J Virol 89:9524–9531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Cell and Molecular Biology Graduate Program, Molecular, Cellular and Integrative Neuroscience Graduate Program, Department of Microbiology, Immunology and Pathology, Prion Research Center, Colorado State University, Fort Collins, CO, 80523, USA

    Julie A. Moreno Ph.D. & Glenn C. Telling M.A. (Oxon), Ph.D.

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  1. Julie A. Moreno Ph.D.
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  2. Glenn C. Telling M.A. (Oxon), Ph.D.
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Correspondence to Glenn C. Telling M.A. (Oxon), Ph.D. .

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  1. Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia

    Victoria A. Lawson

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Moreno, J.A., Telling, G.C. (2017). Insights into Mechanisms of Transmission and Pathogenesis from Transgenic Mouse Models of Prion Diseases. In: Lawson, V. (eds) Prions. Methods in Molecular Biology, vol 1658. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7244-9_16

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