Abstract
Seminal studies showed that optimal disease progression requires matching of the primary structures of PrPSc and PrPC paved the way for the development of Tg models in which to study human prions and subsequently other naturally occurring mammalian prions. Here we review how transgenic mouse models are being used to elucidate basic molecular mechanisms of prion propagation and strain variation, and to address the likelihood of interspecies prion transmissions, in particular the zoonotic potential of various animal prion strains.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Prusiner SB (1998) Prions (Les Prix Nobel Lecture). In: Frängsmyr T (ed) Les prix Nobel. Almqvist & Wiksell International, Stockholm, pp 268–323
Prusiner SB et al (1990) Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63(4):673–686
Scott M et al (1993) Propagation of prions with artificial properties in transgenic mice expressing chimeric PrP genes. Cell 73(5):979–988
Kocisko DA et al (1994) Cell-free formation of protease-resistant prion protein. Nature 370(6489):471–474
Vidal E et al (2015) Transgenic mouse bioassay: evidence that rabbits are susceptible to a variety of prion isolates. PLoS Pathog 11(8):e1004977
Chianini F et al (2012) Rabbits are not resistant to prion infection. Proc Natl Acad Sci U S A 109(13):5080–5085
Westaway D et al (1987) Distinct prion proteins in short and long scrapie incubation period mice. Cell 51(4):651–662
Hunter N et al (2000) Sheep and goats: natural and experimental TSEs and factors influencing incidence of disease. Arch Virol Suppl 16:181–188
Baker HF et al (1991) Amino acid polymorphism in human prion protein and age at death in inherited prion disease. Lancet 337(8752):1286
Collinge J, Palmer MS, Dryden AJ (1991) Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. Lancet 337(8755):1441–1442
Palmer MS et al (1991) Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease. Nature 352(6333):340–342
Nonno R et al (2006) Efficient transmission and characterization of Creutzfeldt-Jakob disease strains in bank voles. PLoS Pathog 2(2):e12
Telling GC et al (1996) Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity. Science 274(5295):2079–2082
Bessen RA, Marsh RF (1994) Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy. J Virol 68(12):7859–7868
Safar J et al (1998) Eight prion strains have PrPSc molecules with different conformations. Nat Med 4(10):1157–1165
Peretz D et al (2002) A change in the conformation of prions accompanies the emergence of a new prion strain. Neuron 34(6):921–932
Collinge J et al (1996) Molecular analysis of prion strain variation and the aetiology of “new variant” CJD. Nature 383(6602):685–690
Hill AF et al (1997) The same prion strain causes vCJD and BSE. Nature 389(6650):448–450
Scott MR et al (2005) Transmission barriers for bovine, ovine, and human prions in transgenic mice. J Virol 79(9):5259–5271
Asante EA 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(23):6358–6366
Korth C 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(8):4784–4789
Scott MR 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
Bruce ME, Dickinson AG (1987) Biological evidence that the scrapie agent has an independent genome. J Gen Virol 68(1):79–89
Collinge J, Clarke AR (2007) A general model of prion strains and their pathogenicity. Science 318(5852):930–936
Haldiman T et al (2013) Co-existence of distinct prion types enables conformational evolution of human PrPSc by competitive selection. J Biol Chem 288(41):29846–29861
Collinge J (1999) Variant Creutzfeldt-Jakob disease. Lancet 354(9175):317–323
Eigen M (1996) On the nature of virus quasispecies. Trends Microbiol 4(6):216–218
Li J et al (2010) Darwinian evolution of prions in cell culture. Science 327(5967):869–872
Angers RC et al (2010) Prion strain mutation determined by prion protein conformational compatibility and primary structure. Science 328(5982):1154–1158
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(16):6028–6033
Makarava N, Baskakov IV (2008) The same primary structure of the prion protein yields two distinct self-propagating states. J Biol Chem 283(23):15988–15996
Rezaei H et al (2002) Amyloidogenic unfolding intermediates differentiate sheep prion protein variants. J Mol Biol 322(4):799–814
Beringue V et al (2012) Facilitated cross-species transmission of prions in extraneural tissue. Science 335(6067):472–475
Rogers 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(8):3182–3186
Chesebro B et al (2005) Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science 308(5727):1435–1439
Telling GC 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(21):9936–9940
Telling GC et al (1995) Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell 83(1):79–90
Perrier V et al (2002) Dominant-negative inhibition of prion replication in transgenic mice. Proc Natl Acad Sci U S A 99(20):13079–13084
Geoghegan JC et al (2009) Trans-dominant inhibition of prion propagation in vitro is not mediated by an accessory cofactor. PLoS Pathog 5(7):e1000535
Christen B 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(5):833–845
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(2):121–128
Telling GC et al (1996) Interactions between wild-type and mutant prion proteins modulate neurodegeneration in transgenic mice. Genes Dev 10(14):1736–1750
Chiesa R 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(10):5574–5579
Bian J et al (2006) GFP-tagged PrP supports compromised prion replication in transgenic mice. Biochem Biophys Res Commun 340(3):894–900
Barmada SJ, Harris DA (2005) Visualization of prion infection in transgenic mice expressing green fluorescent protein-tagged prion protein. J Neurosci 25(24):5824–5832
Shmerling D et al (1998) Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Cell 93(2):203–214
Baumann F et al (2007) Lethal recessive myelin toxicity of prion protein lacking its central domain. EMBO j 26(2):538–547
Li A et al (2007) Neonatal lethality in transgenic mice expressing prion protein with a deletion of residues 105-125. EMBO j 26(2):548–558
Scott M et al (1989) Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques. Cell 59(5):847–857
Angers R et al (2014) Structural effects of PrP polymorphisms on intra- and interspecies prion transmission. Proc Natl Acad Sci U S A 111(30):11169–11174
Telling GC (2010) Nucleic acid-free mutation of prion strains. Prion 4(4):252–255
Büeler H et al (1992) Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356(6370):577–582
Gombojav A et al (2003) Susceptibility of transgenic mice expressing chimeric sheep, bovine and human PrP genes to sheep scrapie. J Vet Med Sci 65(3):341–347
Kupfer L 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(6):704–713
Scott MR 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(26):14279–14284
Bishop MT et al (2006) Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 5(5):393–398
Hadlow WJ (1959) Scrapie and kuru. Lancet 2:289–290
Gajdusek DC, Gibbs CJ Jr, Alpers M (1966) Experimental transmission of a kuru-like syndrome to chimpanzees. Nature 209(5025):794–796
Gibbs CJ Jr et al (1968) Creutzfeldt-Jakob disease (spongiform encephalopathy): transmission to the chimpanzee. Science 161(3839):388–389
Brown P et al (1994) Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol 35(5):513–529
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
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
Tateishi J, Kitamoto T (1995) Inherited prion diseases and transmission to rodents. Brain Pathol 5(1):53–59
Manuelidis E et al (1976) Serial propagation of Creutzfeldt-Jakob disease in guinea pigs. Proc Natl Acad Sci U S A 73(1):223–227
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
Scott MR et al (1992) Chimeric prion protein expression in cultured cells and transgenic mice. Protein Sci 1(8):986–997
Kong Q et al (2008) Evaluation of the human transmission risk of an atypical bovine spongiform encephalopathy prion strain. J Virol 82(7):3697–3701
Beringue V et al (2008) Transmission of atypical bovine prions to mice transgenic for human prion protein. Emerg Infect Dis 14(12):1898–1901
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(26):12005–12010
Hill AF et al (2003) Molecular classification of sporadic Creutzfeldt-Jakob disease. Brain 126(6):1333–1346
Parchi P et al (1996) Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease. Ann Neurol 39(6):767–778
Polymenidou M et al (2005) Coexistence of multiple PrPSc types in individuals with Creutzfeldt-Jakob disease. Lancet Neurol 4(12):805–814
Mastrianni JA et al (2001) Inherited prion disease caused by the V210I mutation: transmission to transgenic mice. Neurology 57(12):2198–2205
Mastrianni J et al (1997) Fatal sporadic insomnia: fatal familial insomnia phenotype without a mutation of the prion protein gene. Neurology 48(Suppl):A296
Notari S et al (2014) Transmission characteristics of variably protease-sensitive prionopathy. Emerg Infect dis 20(12):2006–2014
Diack AB et al (2014) Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties. Emerg Infect Dis 20(12):1969–1979
Giles K et al (2010) Human prion strain selection in transgenic mice. Ann Neurol 68(2):151–161
Will RG et al (1996) A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347(9006):921–925
Collinge J et al (1995) Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature 378(6559):779–783
Mead S et al (2009) Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study. Lancet Neurol 8(1):57–66
Plinston C et al (2011) Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy infection following passage in sheep. J Virol 85(3):1174–1181
Plinston C 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(Pt_8):1855–1859
Asante EA 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(28):10759–10764
Mead S et al (2009) A novel protective prion protein variant that colocalizes with kuru exposure. N Engl J Med 361(21):2056–2065
Asante EA et al (2015) A naturally occurring variant of the human prion protein completely prevents prion disease. Nature 522(7557):478–481
Hsiao K et al (1989) Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome. Nature 338(6213):342–345
Manson JC et al (1999) A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy. EMBO 18(23):6855–6864
Hsiao KK et al (1994) Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein. Proc Natl Acad Sci U S A 91(19):9126–9130
Kaneko K, Ball HL, Wille H, Zhang H, Groth D, Torchia M, Tremblay P, Safar J, Prusiner SB, SJ DA, Baldwin MA, Cohen FE (2000) A synthetic peptide initiates Gerstmann-Straussler-Scheinker (GSS) disease in transgenic mice. J Mol Biol 295(4):997–1007
Tremblay P et al (2004) Mutant PrPSc conformers induced by a synthetic peptide and several prion strains. J Virol 78(4):2088–2099
Cohen FE et al (1994) Structural clues to prion replication. Science 264(5158):530–531
Tzaban S et al (2002) Protease-sensitive scrapie prion protein in aggregates of heterogeneous sizes. Biochemistry 41(42):12868–12875
Korth C et al (1997) Prion (PrPSc)-specific epitope defined by a monoclonal antibody. Nature 389:74–77
Nazor KE et al (2005) Immunodetection of disease-associated mutant PrP, which accelerates disease in GSS transgenic mice. EMBO j 24(13):2472–2480
Uptain SM, Lindquist S (2002) Prions as protein-based genetic elements. Annu Rev Microbiol 56(1):703–741
Piccardo P et al (2013) Dissociation of prion protein amyloid seeding from transmission of a spongiform encephalopathy. J Virol 87(22):12349–12356
Legname G et al (2004) Synthetic mammalian prions. Science 305(5684):673–676
Asante EA et al (2015) Transmission properties of human PrP 102L prions challenge the relevance of mouse models of GSS. PLoS Pathog 11(7):e1004953
Friedman-Levi Y et al (2011) Fatal prion disease in a mouse model of genetic E200K Creutzfeldt-Jakob disease. PLoS Pathog 7(11):e1002350
Chiesa R et al (1998) Neurological illness in transgenic mice expressing a prion protein with an insertional mutation. Neuron 21(6):1339–1351
Chiesa R et al (2003) Molecular distinction between pathogenic and infectious properties of the prion protein. J Virol 77(13):7611–7622
Dossena S et al (2008) Mutant prion protein expression causes motor and memory deficits and abnormal sleep patterns in a transgenic mouse model. Neuron 60(4):598–609
Bouybayoune I et al (2015) Transgenic fatal familial insomnia mice indicate prion infectivity-independent mechanisms of pathogenesis and phenotypic expression of disease. PLoS Pathog 11(4):e1004796
Jackson WS et al (2009) Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice. Neuron 63(4):438–450
Jackson WS 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(36):14759–14764
Hsiao KK et al (1991) A prion protein variant in a family with the telencephalic form of Gerstmann-Sträussler-Scheinker syndrome. Neurology 41(5):681–684
Hegde RS et al (1998) A transmembrane form of the prion protein in neurodegenerative disease. Science 279(5352):827–834
Yang W et al (2009) A new transgenic mouse model of Gerstmann-Straussler-Scheinker syndrome caused by the A117V mutation of PRNP. J Neurosci 29(32):10072–10080
Asante EA 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(9):e1003643
Buschmann A et al (2000) Detection of cattle-derived BSE prions using transgenic mice overexpressing bovine PrP(C). Arch Virol Suppl 16:75–86
Castilla J et al (2003) Early detection of PrPres in BSE-infected bovine PrP transgenic mice. Arch Virol 148(4):677–691
Jacobs JG 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(6):1821–1829
Casalone C 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(9):3065–3070
Richt JA, Hall SM (2008) BSE case associated with prion protein gene mutation. PLoS Pathog 4(9):e1000156
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(5):934–942
Beringue V et al (2006) Isolation from cattle of a prion strain distinct from that causing bovine spongiform encephalopathy. PLoS Pathog 2(10):e112
Beringue V et al (2007) A bovine prion acquires an epidemic bovine spongiform encephalopathy strain-like phenotype on interspecies transmission. J Neurosci 27(26):6965–6971
Buschmann A et al (2006) Atypical BSE in Germany—proof of transmissibility and biochemical characterization. Vet Microbiol 117(2-4):103–116
Capobianco R et al (2007) Conversion of the BASE prion strain into the BSE strain: the origin of BSE? PLoS Pathog 3(3):e31
Wadsworth JD et al (2004) Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science 306(5702):1793–1796
Beringue V et al (2008) Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD. PLoS One 3(1):e1419
Espinosa JC 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(8):1214–1221
Westaway D et al (1994) Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice overexpressing wild-type prion proteins. Cell 76(1):117–129
Rubenstein R et al (2012) PrP(Sc) detection and infectivity in semen from scrapie-infected sheep. J Gen Virol 93(Pt_6):1375–1383
Crozet C et al (2001) Efficient transmission of two different sheep scrapie isolates in transgenic mice expressing the ovine PrP gene. J Virol 75(11):5328–5334
Crozet C et al (2001) Florid plaques in ovine PrP transgenic mice infected with an experimental ovine BSE. EMBO Rep 2(10):952–956
Vilotte JL et al (2001) Markedly increased susceptibility to natural sheep scrapie of transgenic mice expressing ovine prp. J Virol 75(13):5977–5984
Tamguney G et al (2009) Transmission of scrapie and sheep-passaged bovine spongiform encephalopathy prions to transgenic mice expressing elk prion protein. J Gen Virol 90(4):1035–1047
Goldmann W 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(5):989–995
Cordier C et al (2006) Transmission and characterization of bovine spongiform encephalopathy sources in two ovine transgenic mouse lines (TgOvPrP4 and TgOvPrP59). J Gen Virol 87(12):3763–3771
Saijo E et al (2013) Epigenetic dominance of prion conformers. PLoS Pathog 9(10):e1003692
Foster JD, Dickinson AG (1988) The unusual properties of CH 1641, a sheep-passaged isolate of scrapie. Vet Rec 123(1):5–8
Baron T, Biacabe AG (2007) Molecular behaviors of “CH1641-like” sheep scrapie isolates in ovine transgenic mice (TgOvPrP4). J Virol 81(13):7230–7237
Kang HE et al (2012) Characterization of conformation-dependent prion protein epitopes. J Biol Chem 287(44):37219–37232
Bencsik A et al (2007) Scrapie strain transmission studies in ovine PrP transgenic mice reveal dissimilar susceptibility. Histochem Cell Biol 127(5):531–539
Baron T 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(12):6243–6251
Le Dur A 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(44):16031–16036
Simmons MM et al (2007) Experimental transmission of atypical scrapie to sheep. BMC Vet Res 3(1):20
Wadsworth JD et al (2013) Atypical scrapie prions from sheep and lack of disease in transgenic mice overexpressing human prion protein. Emerg Infect Dis 19(11):1731–1739
Cassard H et al (2014) Evidence for zoonotic potential of ovine scrapie prions. Nat Commun 5:5821
Mathiason CK et al (2006) Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 314(5796):133–136
Browning SR et al (2004) Transmission of prions from mule deer and elk with chronic wasting disease to transgenic mice expressing cervid PrP. J Virol 78(23):13345–13350
Bartz JC et al (1998) The host range of chronic wasting disease is altered on passage in ferrets. Virology 251(2):297–301
Angers RC et al (2006) Prions in skeletal muscles of deer with chronic wasting disease. Science 311(5764):1117–1117
Meade-White K et al (2007) Resistance to chronic wasting disease in transgenic mice expressing a naturally occurring allelic variant of deer prion protein. J Virol 81(9):4533–4539
LaFauci G et al (2006) Passage of chronic wasting disease prion into transgenic mice expressing Rocky Mountain elk (Cervus elaphus Nelsoni) PrPC. J Gen Virol 87(12):3773–3780
Tamguney G et al (2006) Transmission of elk and deer prions to transgenic mice. J Virol 80(18):9104–9114
Kong Q et al (2005) Chronic wasting disease of elk: transmissibility to humans examined by transgenic mouse models. J Neurosci 25(35):7944–7949
Sigurdson CJ et al (2006) Strain fidelity of chronic wasting disease upon murine adaptation. J Virol 80(24):12303–12311
Raymond GJ et al (2007) Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains. J Virol 81(8):4305–4314
Meyerett C et al (2008) In vitro strain adaptation of CWD prions by serial protein misfolding cyclic amplification. Virology 382(2):267–276
Green KM et al (2008) Accelerated high fidelity prion amplification within and across prion species barriers. PLoS Pathog 4(8):e1000139
Kurt TD et al (2007) Efficient in vitro amplification of chronic wasting disease PrPRES. J Virol 81(17):9605–9608
Kurt TD et al (2009) Trans-species amplification of PrP(CWD) and correlation with rigid loop 170N. Virology 387(1):235–243
Haley NJ et al (2009) Detection of CWD prions in urine and saliva of deer by transgenic mouse bioassay. PLoS One 4(3):e4848
Tamguney G et al (2009) Asymptomatic deer excrete infectious prions in faeces. Nature 461(7263):529–532
Haley NJ 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(11):e7990
Pulford B 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(2):425–434
Henderson DM et al (2013) Rapid Antemortem detection of CWD prions in deer saliva. PLoS One 8(9):e74377
Angers RC et al (2009) Chronic wasting disease prions in elk antler velvet. Emerg Infect Dis 15(5):696–703
Race B et al (2009) Prion infectivity in fat of deer with chronic wasting disease. J Virol 83(18):9608–9610
Johnson C 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(3):576–581
Raymond GJ et al (2000) Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease. EMBO J 19(17):4425–4430
Heaton MP et al (2003) Prion gene sequence variation within diverse groups of U.S. sheep, beef cattle, and deer. Mamm Genome 14(11):765–777
O’Rourke KI 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(5):1339–1346
Schatzl HM et al (1997) Is codon 129 of prion protein polymorphic in human beings but not in animals? Lancet 349(9065):1603–1604
O'Rourke KI et al (1998) Monoclonal antibody F89/160.1.5 defines a conserved epitope on the ruminant prion protein. J Clin Microbiol 36(6):1750–1755
O'Rourke KI et al (1999) PrP genotypes of captive and free-ranging Rocky Mountain elk (Cervus elaphus Nelsoni) with chronic wasting disease. J Gen Virol 80(10):2765–2679
Hamir AN 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(1):110–114
O'Rourke KI et al (2007) Elk with a long incubation prion disease phenotype have a unique PrPd profile. Neuroreport 18(18):1935–1938
Green KM et al (2008) The elk PRNP codon 132 polymorphism controls cervid and scrapie prion propagation. J Gen Virol 89(2):598–608
Race B et al (2011) In vivo comparison of chronic wasting disease infectivity from deer with variation at prion protein residue 96. J Virol 85(17):9235–9238
Keane DP et al (2008) Chronic wasting disease in a Wisconsin white-tailed deer farm. J Vet Diagn Investig 20(5):698–703
Duque Velasquez C et al (2015) Deer prion proteins modulate the emergence and adaptation of chronic wasting disease strains. J Virol 89(24):12362–12373
Gossert AD et al (2005) Prion protein NMR structures of elk and of mouse/elk hybrids. Proc Natl Acad Sci U S A 102(3):646–650
Sigurdson CJ et al (2009) De novo generation of a transmissible spongiform encephalopathy by mouse transgenesis. Proc Natl Acad Sci U S A 106(1):304–309
Kurt TD et al (2014) Prion transmission prevented by modifying the beta2-alpha2 loop structure of host PrPC. J Neurosci 34(3):1022–1027
Sigurdson CJ et al (2010) A molecular switch controls interspecies prion disease transmission in mice. J Clin Invest 120(7):2590–2599
Kurt TD et al (2015) Human prion protein sequence elements impede cross-species chronic wasting disease transmission. J Clin Invest 125(4):1485–1496
Khan MQ 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(46):19808–19813
Jewell JE et al (2005) Low frequency of PrP genotype 225SF among free-ranging mule deer (Odocoileus hemionus) with chronic wasting disease. J Gen Virol 86(8):2127–2134
Wolfe LL, Fox KA, Miller MW (2014) “atypical” chronic wasting disease in PRNP genotype 225FF mule deer. J Wildl Dis 50(3):660–665
Johnson C et al (2006) Prion protein polymorphisms in white-tailed deer influence susceptibility to chronic wasting disease. J Gen Virol 87(7):2109–2114
Bessen RA et al (2011) Transmission of chronic wasting disease identifies a prion strain causing cachexia and heart infection in hamsters. PLoS One 6(12):e28026
Crowell J et al (2015) Host determinants of prion strain diversity independent of prion protein genotype. J Virol 89(20):10427–10441
Bruce ME et al (1997) Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389(6650):498–501
Belay ED et al (2004) Chronic wasting disease and potential transmission to humans. Emerg Infect Dis 10(6):977–984
Mawhinney S et al (2006) Human prion disease and relative risk associated with chronic wasting disease. Emerg Infect Dis 12(10):1527–1535
Barria MA et al (2011) Generation of a new form of human PrP(Sc) in vitro by interspecies transmission from cervid prions. J Biol Chem 286(9):7490–7495
Sandberg M et al (2010) Chronic wasting disease prions are not transmissible to transgenic mice over-expressing human prion protein. J Gen Virol 91(10):2651–2657
Marsh RF et al (2005) Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus). J Virol 79(21):13794–13796
Race B et al (2009) Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis 15(9):1366–1376
Davenport KA et al (2015) Insights into chronic wasting disease and bovine spongiform encephalopathy species barriers by use of real-time conversion. J Virol 89(18):9524–9531
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Science+Business Media LLC
About this protocol
Cite this protocol
Moreno, J., Telling, G.C. (2017). Transgenic Mouse Models of Prion Diseases. In: Liberski, P. (eds) Prion Diseases. Neuromethods, vol 129. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7211-1_16
Download citation
DOI: https://doi.org/10.1007/978-1-4939-7211-1_16
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-7209-8
Online ISBN: 978-1-4939-7211-1
eBook Packages: Springer Protocols