title: Peripheral circulation of the prion infectious agent in transgenic mice expressing the ovine prion protein gene in neurons only.
abstract: BACKGROUND
  For prion diseases, even if a large body of evidence indicates that both the lymphoreticular system (LRS) and peripheral nerves are involved in scrapie neuroinvasion, the processes by which prions invade the central nervous system are only partially understood.
  
  
  METHODS
  Transgenic Tg(OvPrP4) mice, which express the ovine prion protein (PrP) gene under the rat neuron-specific enolase promoter on a knockout background, were used to study prion extracerebral circulation after scrapie prions were inoculated via the intracerebral (ic) and the intraperitoneal (ip) route.
  
  
  RESULTS
  Surprisingly, PrP(Sc) was detected in the spleens of mice inoculated ic with prions. Moreover, the absence of the ovine PrP(C) in nonneural tissue at the periphery did not stop neuroinvasion after ip challenge. Additionally, pilot studies performed in Tg(OvPrP4) mice that had undergone splenectomy before ic prion inoculation showed that the time course of the disease is delayed.
  
  
  CONCLUSIONS
  Given that these mice express the ovine PrP gene in neuronal cells but not in nonnervous tissue, our results suggest that PrP(C) expressed by cells of the LRS are not necessary for neuroinvasion or for their ability to accumulate PrP(Sc) and emphasize the importance of extracerebral circulation of PrP(C) or PrP(Sc) for the development of the disease.
authors.affiliation: Agence Francaise de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, Lyon, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Crozet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lezmi
authors.forename: Fréderic
authors.initials: F
authors.lastname: Flamant
authors.forename: Jacques
authors.initials: J
authors.lastname: Samarut
authors.forename: Thierry
authors.initials: T
authors.lastname: Baron
authors.forename: Anna
authors.initials: A
authors.lastname: Bencsik
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D007267:Injections; D007274:Injections, Intraperitoneal; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010525:Peripheral Nerves / Q000473:pathology; D018620:PrPSc Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012608:Scrapie / Q000635:transmission*; D012756:Sheep
chemical_list: D018620:PrPSc Proteins; D012333:RNA, Messenger