TY - JOUR
T1 - Peripheral circulation of the prion infectious agent in transgenic mice expressing the ovine prion protein gene in neurons only
AU - Crozet, Carole
AU - Lezmi, Stéphane
AU - Flamant, Frédéric
AU - Samarut, Jacques
AU - Baron, Thierry
AU - Bencsik, Anna
N1 - Funding Information:
Received 16 August 2006; accepted 2 November 2006; electronically published 16 February 2007. Potential conflicts of interest: none reported. Presented in part: Keystone Symposia: Molecular Aspects of Transmissible Spongiform Encephalopathies (Prion Diseases), Breckenridge, Colorado, 2–6 April 2003 (abstract 123). Financial support: La Fondation pour la Recherche Médicale (grant to C.C.). a Present affiliation: Institut de Génétique Humaine, UPR1142 Centre National de la Recherche Scientifique, Montpellier, France. Reprints or correspondence: Dr. Anna Bencsik, AFSSA, Unité ATNC, 31 ave. Tony Garnier, 69364 Lyon, France (a.bencsik@lyon.afssa.fr).
PY - 2007/4/1
Y1 - 2007/4/1
N2 - 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.
AB - 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.
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U2 - 10.1086/512085
DO - 10.1086/512085
M3 - Article
C2 - 17330790
AN - SCOPUS:33947386271
SN - 0022-1899
VL - 195
SP - 997
EP - 1006
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 7
ER -