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J Gen Virol 88 (2007), 1842-1849; DOI 10.1099/vir.0.82568-0

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Reduced susceptibility to bovine spongiform encephalopathy prions in transgenic mice expressing a bovine PrP with five octapeptide repeats

Alejandro Brun1, Alfonso Gutiérrez-Adán2, Joaquín Castilla1,{dagger}, Belén Pintado2, Fayna Díaz-San Segundo1,{ddagger}, María J. Cano1, Elia Alamillo1, Juan C. Espinosa1 and Juan M. Torres1

1 Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid, Spain
2 Departamento de Reproducción Animal y Conservación de Recursos Zoogenéticos, 28049 Madrid, Spain

Correspondence
Juan M. Torres
jmtorres{at}inia.es

In this work, transgenic (Tg) mice were generated expressing a bovine prion protein containing five octarepeats (BoPrP5OR-Tg). After intracerebral inoculation of bovine spongiform encephalopathy (BSE) inoculum, these mice suffered a BSE-like neuropathology but survived longer compared with homologous Tg mice expressing similar levels of a six octarepeat BoPrP protein (BoPrP6OR-Tg). De novo-generated five octarepeat (5OR) PrPSc showed no biochemical differences from 6OR-PrPSc, and the proteinase K-resistant core (PrPres) was biochemically indistinguishable from the 6OR counterpart. Lower susceptibility to BSE is suggested for BoPrP5OR-Tg mice, as they were not as efficient at replicating BSE prions from the same natural source inoculum as BoPrP6OR-Tg mice expressing similar PrPC levels. These results raise the possibility of selecting cattle breeds bearing the 5OR Prnp allele that are less susceptible to prion infection.

{dagger}Present address: Department of Infectology, The Scripps Research Institute, 5353 Parkside Drive, Jupiter, FL 33458, USA.

{ddagger}Present address: Plum Island Animal Disease Centre, ARS, USDA, PO Box 848, Greenport, NY 11944, USA.






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