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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.

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