Reduced susceptibility to bovine spongiform encephalopathy prions in transgenic mice expressing a bovine PrP with five octapeptide repeats.
In this work, transgenic (Tg) mice were generated expressing a bovine prion protein containing five octarepeats (BoPrP(5OR)-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 (BoPrP(6OR)-Tg). De novo-generated five octarepeat (5OR) PrP(Sc) showed no biochemical differences from 6OR-PrP(Sc), and the proteinase K-resistant core (PrP(res)) was biochemically indistinguishable from the 6OR counterpart. Lower susceptibility to BSE is suggested for BoPrP(5OR)-Tg mice, as they were not as efficient at replicating BSE prions from the same natural source inoculum as BoPrP(6OR)-Tg mice expressing similar PrP(C) levels. These results raise the possibility of selecting cattle breeds bearing the 5OR Prnp allele that are less susceptible to prion infection.
Brun
Alejandro
A
Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid, Spain.
Gutiérrez-Adán
Alfonso
A
Departamento de Reproducción Animal y Conservación de Recursos Zoogenéticos, 28049 Madrid, Spain.
Castilla
Joaquín
J
Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid, Spain.
Pintado
Belén
B
Departamento de Reproducción Animal y Conservación de Recursos Zoogenéticos, 28049 Madrid, Spain.
Díaz-San Segundo
Fayna
F
Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid, Spain.
Cano
María J
MJ
Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid, Spain.
Alamillo
Elia
E
Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid, Spain.
Espinosa
Juan C
JC
Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid, Spain.
Torres
Juan M
JM
Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid, Spain.
D000818:Animals; D001921:Brain / Q000473:pathology; D002417:Cattle; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D016643:Encephalopathy, Bovine Spongiform / Q000235:genetics* / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D011328:Prions / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*
D011328:Prions