QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, May 26, 2004, 24(21):5063-5069; doi:10.1523/JNEUROSCI.5400-03.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Castilla, J. Articles by Torres, J. M. Search for Related Content PubMed PubMed Citation Articles by Castilla, J. Articles by Torres, J. M.

 Previous Article  |  Next Article 

Neurobiology of Disease
Subclinical Bovine Spongiform Encephalopathy Infection in Transgenic Mice Expressing Porcine Prion Protein

Joaquín Castilla,¹ Alfonso Gutiérrez-Adán,² Alejandro Brun,¹ Deirdre Doyle,³ Belén Pintado,² Miguel A. Ramírez,² Francisco J. Salguero,¹ Beatriz Parra,¹ Fayna Díaz San Segundo,¹ José M. Sánchez-Vizcaíno,¹ Mark Rogers,³ and Juan M. Torres¹

¹Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Valdeolmos, 28130 Madrid, Spain, ²Departamento de Reproducción Animal y Conservación de Recursos Zoogenéticos, 28040 Madrid, Spain, and ³Department of Zoology and Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland

The bovine-porcine species barrier to bovine spongiform encephalopathy (BSE) infection was explored by generating transgenic mouse lines expressing the porcine prion protein (PrP) gene. All of the porcine transgenic (poTg) mice showed clinical signs of BSE after intracerebral inoculation with a high-titer BSE inoculum. The protease-resistant PrP (PrP^res) was detected in 14% (3 of 22) of the BSE-infected poTg mice by immunohistochemical or immunoblot analysis. Despite being able to infect 42% (5 of 12) of control mice, a low-dose BSE inoculum failed to penetrate the species barrier in our poTg mouse model. The findings of these infectivity studies suggest that there is a strong species barrier between cows and pigs. However, after second-passage infection of poTg mice using brain homogenates of BSE-inoculated mice scoring negative for the incoming prion protein as inoculum, it was possible to detect the presence of the infectious agent. Thus, porcine-adapted BSE inocula were efficient at infecting poTg mice, giving rise to an incubation period substantially reduced from 300 to 177 d after inoculation and to the presence of PrP^res in 100% (21 of 21) of the mice. We were therefore able to conclude that initial exposure to the bovine prion may lead to subclinical infection such that brain homogenates from poTg mice classified as uninfected on the basis of the absence of PrP^res are infectious when used to reinoculate poTg mice. Collectively, our findings suggest that these poTg mice could be used as a sensitive bioassay model for prion detection in pigs.

Key words: BSE transmission; porcine prion; PrP; scrapie; transgenic mice; species barrier

---

Received Dec 7, 2003; revised April 7, 2004; accepted April 9, 2004.

This article has been cited by other articles:

				C A Heath, R A Barker, T F G Esmonde, P Harvey, R Roberts, P Trend, M W Head, C Smith, J E Bell, J W Ironside, et al. Dura mater-associated Creutzfeldt-Jakob disease: experience from surveillance in the UK J. Neurol. Neurosurg. Psychiatry, July 1, 2006; 77(7): 880 - 882. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help