Brun Alejandro, Gutiérrez-Adán Alfonso, Castilla Joaquín, Pintado Belén, Díaz-San Segundo Fayna, Cano María J, Alamillo Elia, Espinosa Juan C, Torres Juan M
Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid, Spain.
Departamento de Reproducción Animal y Conservación de Recursos Zoogenéticos, 28049 Madrid, Spain.
J Gen Virol. 2007 Jun;88(Pt 6):1842-1849. doi: 10.1099/vir.0.82568-0.
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.
在本研究中，构建了表达含有五个八肽重复序列的牛朊蛋白的转基因（Tg）小鼠（BoPrP(5OR)-Tg）。经脑内接种牛海绵状脑病（BSE）接种物后，这些小鼠出现了类似BSE的神经病理学变化，但与表达相似水平的含有六个八肽重复序列的牛朊蛋白的同源Tg小鼠（BoPrP(6OR)-Tg）相比，存活时间更长。新生的五个八肽重复序列（5OR）的PrP(Sc)与6OR-PrP(Sc)在生化性质上无差异，且蛋白酶K抗性核心（PrP(res)）在生化性质上与6OR对应物无法区分。BoPrP(5OR)-Tg小鼠对BSE的易感性较低，因为它们在从相同天然来源接种物中复制BSE朊病毒方面不如表达相似PrP(C)水平的BoPrP(6OR)-Tg小鼠有效。这些结果增加了选择携带5OR Prnp等位基因、对朊病毒感染敏感性较低的牛品种的可能性。
