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Volume 19, Number 12—December 2013

Research

Spontaneous Generation of Infectious Prion Disease in Transgenic Mice

Juan-María TorresComments to Author , Joaquín Castilla, Belén Pintado, Alfonso Gutiérrez-Adan, Olivier Andréoletti, Patricia Aguilar-Calvo, Ana-Isabel Arroba, Beatriz Parra-Arrondo, Isidro Ferrer, Jorge Manzanares, and Juan-Carlos Espinosa
Author affiliations: Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Madrid, Spain (J.-M. Torres, J. Castilla, B. Pintado, A. Gutiérrez-Adán P. Aguilar-Calvo, A.-I. Arroba, B. Parra-Arrondo, J.-C. Espinosa); Basque Foundation for Science, Bilbao, Spain (J. Castilla); Ecole Nationale Vétérinaire de Toulouse, Toulouse, France (O. Andréoletti); Hospitalet de Llobregat, Barcelona, Spain (I. Ferrer); Universidad Miguel Hernandez, Sant Joan d´Alacant, Spain (J. Manzanares)

Main Article

Table 2

Infectivity of 113LBoPrP-Tg037 mice brain homogenates in BoPrP-Tg110*

Inoculum Mean ± SEM survival time, days (no. diseased/no. tested)†
First passage Second passage Third passage
113LBoPrP-Tg037 (179 d old)‡ 330 (1/5) 272 ± 38 (6/6) 252 ± 23 (6/6)
113LBoPrP-Tg037-pool (150–250 d old)§ 322, 406 (2/6) 291 ± 23 (6/6) 255 ± 14 (7/7)
wtBoPrP-Tg110-pool (500–600 d old) >650 (0/12) >650 (0/12) NA
Normal mouse brain (500–600 d old) >650 (0/12) >650 (0/12) NA
Classical BSE-C (VLAPG817/00) ¶ 295 ± 12 (6/6) 265 ± 35 (6/6) NA
Atypical BSE-H (CASE 03–2095)# 292 ± 5 (6/6) 296 ± 7 (6/6) NA
Atypical BSE-L (02.2528)** 207 ± 7 (6/6) 199 ± 1 (6/6) NA

*BoPrP, bovine prion protein; 113L, leucine substitution at codon 113; wtBoPrP, wild-type bovine prion protein; NA, not available; BSE, bovine spongiform encephalopathy.
†Intracerebral inoculation with 2 mg brain tissue equivalent in BoPrP-Tg110+/+ (8× expression level).
‡Brain homogenate from a unique terminally sick animal.
§Brain homogenate from a pool of 5 terminally sick mice that died at 150–250 d of age.
¶Brainstem homogenate of 1 cow naturally infected with classical BSE (RQ 225:PG817/00) supplied by the Veterinary Laboratories Agency (New Haw,
#Data from Torres et al. (31).
**Brainstem samples from naturally affected cows given a diagnosis of atypical BSE-L by the Agence Française de Sécurité Sanitaire des Aliments (Lyon, France).

Main Article

References
  1. Griffith  JS. Self-replication and scrapie. Nature. 1967;215:1043–4 . DOIPubMedGoogle Scholar
  2. McKinley  MP, Bolton  DC, Prusiner  SB. A protease-resistant protein is a structural component of the scrapie prion. Cell. 1983;35:57–62 . DOIPubMedGoogle Scholar
  3. Prusiner  SB. Novel proteinaceous infectious particles cause scrapie. Science. 1982;216:136–44. DOIPubMedGoogle Scholar
  4. Prusiner  SB. Molecular biology of prion diseases. Science. 1991;252:1515–22. DOIPubMedGoogle Scholar
  5. Brown  P, Gibbs  CJ Jr, Rodgers-Johnson  P, Asher  DM, Sulima  MP, Bacote  A, Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol. 1994;35:513–29. DOIPubMedGoogle Scholar
  6. Tateishi  J, Kitamoto  T, Hoque  MZ, Furukawa  H. Experimental transmission of Creutzfeldt-Jakob disease and related diseases to rodents. Neurology. 1996;46:532–7. DOIPubMedGoogle Scholar
  7. Mastrianni  JA, Capellari  S, Telling  GC, Han  D, Bosque  P, Prusiner  SB, Inherited prion disease caused by the V210I mutation: transmission to transgenic mice. Neurology. 2001;57:2198–205. DOIPubMedGoogle Scholar
  8. Nonno  R, Bari  MA, Cardone  F, Vaccari  G, Fazzi  P, Dell’omo  G, Efficient transmission and characterization of Creutzfeldt-Jakob disease strains in bank voles. PLoS Pathog. 2006;2:e12.. DOIPubMedGoogle Scholar
  9. Collinge  J, Palmer  MS. Prion diseases. Curr Opin Genet Dev. 1992;2:448–54. DOIPubMedGoogle Scholar
  10. Collinge  J. Molecular neurology of prion disease. J Neurol Neurosurg Psychiatry. 2005;76:906–19. DOIPubMedGoogle Scholar
  11. Collinge  J, Clarke  AR. A general model of prion strains and their pathogenicity. Science. 2007;318:930–6. DOIPubMedGoogle Scholar
  12. Chiesa  R, Drisaldi  B, Quaglio  E, Migheli  A, Piccardo  P, Ghetti  B, 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. 2000;97:5574–9. DOIPubMedGoogle Scholar
  13. Castilla  J, Gutierrez-Adan  A, Brun  A, Pintado  B, Salguero  FJ, Parra  B, Transgenic mice expressing bovine PrP with a four extra repeat octapeptide insert mutation show a spontaneous, non-transmissible, neurodegenerative disease and an expedited course of BSE infection. FEBS Lett. 2005;579:6237–46. DOIPubMedGoogle Scholar
  14. Chiesa  R, Piccardo  P, Quaglio  E, Drisaldi  B, Si-Hoe  SL, Takao  M, Molecular distinction between pathogenic and infectious properties of the prion protein. J Virol. 2003;77:7611–22. DOIPubMedGoogle Scholar
  15. Hsiao  KK, Scott  M, Foster  D, Groth  DF, DeArmond  SJ, Prusiner  SB. Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science. 1990;250:1587–90. DOIPubMedGoogle Scholar
  16. Jackson  WS, Borkowski  AW, Faas  H, Steele  AD, King  OD, Watson  N, Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice. Neuron. 2009;63:438–50. DOIPubMedGoogle Scholar
  17. Sigurdson  CJ, Nilsson  KP, Hornemann  S, Heikenwalder  M, Manco  G, Schwarz  P, De novo generation of a transmissible spongiform encephalopathy by mouse transgenesis. Proc Natl Acad Sci U S A. 2009;106:304–9. DOIPubMedGoogle Scholar
  18. Hsiao  K, Baker  HF, Crow  TJ, Poulter  M, Owen  F, Terwilliger  JD, Linkage of a prion protein missense variant to Gerstmann–Sträussler syndrome. Nature. 1989;338:342–5. DOIPubMedGoogle Scholar
  19. Ikeda  SI, Yanagisawa  N, Glenner  GG, Allsop  D. Gerstmann–Sträussler–Scheinker disease showing protein amyloid deposits in the peripheral regions of PrP immunoreactive amyloid plaques. Neurodegeneration. 1992;1:281–8.
  20. Castilla  J, Gutierrez Adan  A, Brun  A, Pintado  B, Ramirez  MA, Parra  B, Early detection of PrP(res) in BSE-infected bovine PrP transgenic mice. Arch Virol. 2003;148:677–91. DOIPubMedGoogle Scholar
  21. Borchelt  DR, Davis  J, Fischer  M, Lee  MK, Slunt  HH, Ratovitsky  T, A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet Anal. 1996;13:159–63. DOIPubMedGoogle Scholar
  22. Castilla  J, Gutierrez-Adan  A, Brun  A, Pintado  B, Parra  B, Ramirez  MA, Different behavior toward bovine spongiform encephalopathy infection of bovine prion protein transgenic mice with one extra repeat octapeptide insert mutation. J Neurosci. 2004;24:2156–64. DOIPubMedGoogle Scholar
  23. Sisó  S, Puig  B, Varea  R, Vidal  E, Acin  C, Prinz  M, Abnormal synaptic protein expression and cell death in murine scrapie. Acta Neuropathol. 2002;103:615–26. DOIPubMedGoogle Scholar
  24. Padilla  D, Béringue  V, Espinosa  JC, Andreoletti  O, Jaumain  E, Reine  F, Sheep and goat BSE propagate more efficiently than cattle BSE in human PrP transgenic mice. PLoS Pathog. 2011;7:e1001319. DOIPubMedGoogle Scholar
  25. Féraudet  C, Morel  N, Simon  S, Volland  H, Frobert  Y, Creminon  C, Screening of 145 anti-PrP monoclonal antibodies for their capacity to inhibit PrPSc replication in infected cells. J Biol Chem. 2005;280:11247–58. DOIPubMedGoogle Scholar
  26. Yull  HM, Ritchie  DL, Langeveld  JP, van Zijderveld  FG, Bruce  ME, Ironside  JW, Detection of type 1 prion protein in variant Creutzfeldt-Jakob disease. Am J Pathol. 2006;168:151–7. DOIPubMedGoogle Scholar
  27. Andréoletti  O, Lacroux  C, Chabert  A, Monnereau  L, Tabouret  G, Lantier  F, PrP(Sc) accumulation in placentas of ewes exposed to natural scrapie: influence of foetal PrP genotype and effect on ewe-to-lamb transmission. J Gen Virol. 2002;83:2607–16 .PubMedGoogle Scholar
  28. Fraser  H, Dickinson  AG. The sequential development of the brain lesion of scrapie in three strains of mice. J Comp Pathol. 1968;78:301–11. DOIPubMedGoogle Scholar
  29. Andréoletti  O, Simon  S, Lacroux  C, Morel  N, Tabouret  G, Chabert  A, PrP(Sc) accumulation in myocytes from sheep incubating natural scrapie. Nat Med. 2004;10:591–3. DOIPubMedGoogle Scholar
  30. Brun  A, Castilla  J, Ramirez  MA, Prager  K, Parra  B, Salguero  FJ, Proteinase K enhanced immunoreactivity of the prion protein-specific monoclonal antibody 2A11. Neurosci Res. 2004;48:75–83. DOIPubMedGoogle Scholar
  31. Torres  JM, Andreoletti  O, Lacroux  C, Prieto  I, Lorenzo  P, Larska  M, Classical bovine spongiform encephalopathy by transmission of H-type prion in homologous prion protein context. Emerg Infect Dis. 2011;17:1636–44. DOIPubMedGoogle Scholar
  32. Espinosa  JC, Andreoletti  O, Castilla  J, Herva  ME, Morales  M, Alamillo  E, Sheep-passaged bovine spongiform encephalopathy agent exhibits altered pathobiological properties in bovine-PrP transgenic mice. J Virol. 2007;81:835–43. DOIPubMedGoogle Scholar
  33. Bruce  ME, McConnell  I, Fraser  H, Dickinson  AG. The disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis. J Gen Virol. 1991;72:595–603. DOIPubMedGoogle Scholar
  34. Priola  SA, Chesebro  B. Abnormal properties of prion protein with insertional mutations in different cell types. J Biol Chem. 1998;273:11980–5. DOIPubMedGoogle Scholar
  35. Hsiao  KK, Groth  D, Scott  M, Yang  SL, Serban  H, Rapp  D, Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein. Proc Natl Acad Sci U S A. 1994;91:9126–30. DOIPubMedGoogle Scholar
  36. Telling  GC, Haga  T, Torchia  M, Tremblay  P, DeArmond  SJ, Prusiner  SB. Interactions between wild-type and mutant prion proteins modulate neurodegeneration in transgenic mice. Genes Dev. 1996;10:1736–50. DOIPubMedGoogle Scholar
  37. Manson  JC, Jamieson  E, Baybutt  H, Tuzi  NL, Barron  R, McConnell  I, A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy. EMBO J. 1999;18:6855–64. DOIPubMedGoogle Scholar
  38. Asante  EA, Gowland  I, Grimshaw  A, Linehan  JM, Smidak  M, Houghton  R, Absence of spontaneous disease and comparative prion susceptibility of transgenic mice expressing mutant human prion proteins. J Gen Virol. 2009;90:546–58. DOIPubMedGoogle Scholar
  39. Nicholson  EM, Brunelle  BW, Richt  JA, Kehrli  ME Jr, Greenlee  JJ. Identification of a heritable polymorphism in bovine PRNP associated with genetic transmissible spongiform encephalopathy: evidence of heritable BSE. PLoS ONE. 2008;3:e2912. DOIPubMedGoogle Scholar
  40. Stöhr  J, Watts  JC, Legname  G, Oehler  A, Lemus  A, Nguyen  HO, Spontaneous generation of anchorless prions in transgenic mice. Proc Natl Acad Sci U S A. 2011;108:21223–8 . DOIPubMedGoogle Scholar

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