Reduced susceptibility to bovine spongiform encephalopathy prions in transgenic mice expressing a bovine PrP with five octapeptide repeats
Reduced susceptibility to bovine spongiform encephalopathy prions in transgenic mice expressing a bovine PrP with five octapeptide repeats
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DOI：
10.1099/vir.0.82568-0
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发表时间：
2007-06-01
影响因子：
3.8
通讯作者：
Torres, Juan M.
中科院分区：
文献类型：
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作者：
Brun, Alejandro;Gutierrez-Adan, Alfonso;Torres, Juan M.
在这项工作中，产生了转基因（Tg）小鼠，表达含有五个八重体的牛朊蛋白（BoPrP(5OR)-Tg）。在脑内接种牛海绵状脑病（BSE）疫苗后，这些小鼠出现了类似疯牛病的神经病理，但与表达相似水平的六八重BoPrP蛋白（BoPrP(6OR)-Tg）的同源Tg小鼠相比，存活时间更长。新生成的5 -八羧酸（5OR） PrPSc与6OR-PrPSc没有生化差异，蛋白酶k抗性核心（PrPres）与6OR对应物在生化上没有区别。BoPrP(5OR)-Tg小鼠对疯牛病的易感性较低，因为与表达相似PrPC水平的BoPrP(6OR)-Tg小鼠相比，BoPrP(5OR)-Tg小鼠从相同的自然来源接种物中复制疯牛病朊病毒的效率较低。这些结果提高了选择携带5OR Prnp等位基因的牛品种不易受朊病毒感染的可能性。
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) 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 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 PrPC levels. These results raise the possibility of selecting cattle breeds bearing the 5OR Prnp allele that are less susceptible to prion infection.