Peripheral circulation of the prion infectious agent in transgenic mice expressing the ovine prion protein gene in neurons only

Carole Crozet, Stéphane Lezmi, Frédéric Flamant, Jacques Samarut, Thierry Baron, Anna Bencsik

Research output: Contribution to journalArticlepeer-review

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, PrPSc was detected in the spleens of mice inoculated ic with prions. Moreover, the absence of the ovine PrPC 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 PrPC expressed by cells of the LRS are not necessary for neuroinvasion or for their ability to accumulate PrPSc and emphasize the importance of extracerebral circulation of PrPC or PrPSc for the development of the disease.

Original languageEnglish (US)
Pages (from-to)997-1006
Number of pages10
JournalJournal of Infectious Diseases
Volume195
Issue number7
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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