Early detection of PRPres in BSE-infected bovine PrP transgenic mice
Early detection of PRPres in BSE-infected bovine PrP transgenic mice
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DOI：
10.1007/s00705-002-0958-4
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发表时间：
2003-04-01
影响因子：
2.7
通讯作者：
Torres, JM
中科院分区：
文献类型：
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作者：
Castilla, J;Adán, AG;Torres, JM
产生了表达不同水平牛朊蛋白基因（boPrP(C)）的转基因小鼠系。在感染疯牛病朊病毒后，所有转基因品系都表现出牛疾病的特征。组织病理学观察到典型的中枢神经系统海绵状变性，Western blot和免疫组化（IHC）检测均可检测到PrPres的存在，证实该模型不存在疯牛病感染的种间屏障。接种后孵育时间的差异取决于接种物中boPrP(C)的表达水平和朊病毒的数量。在无临床症状的情况下，免疫组化和免疫印迹分析分别可在接种后150天和196天检测到疾病的病理特征标志物。这一结果表明，通过免疫评估PrPres在接种动物大脑中的存在，可以更早地测量实验性小鼠生物测定中的朊病毒传染性。虽然这些转基因小鼠也易受羊痒病朊病毒感染，但孵育时间要长得多，而且只有70%的接种小鼠检测到PrPres。有趣的是，转基因小鼠传播的羊痒病朊病毒与原始羊痒病和转基因小鼠传播的疯牛病疫苗相比，表现出不同的生化特性。
Transgenic mouse lines expressing different levels of the bovine prion protein gene (boPrP(C)) were generated. Upon infection with BSE prions, all transgenic lines tested exhibited characteristics of the bovine disease. Typical CNS spongiform degeneration was observed by histopathology and presence of PrPres could be detected both by Western blot and immunohistochemistry (IHC) assays, confirming for this model the absence of an interspecies barrier to BSE infection. Differences in incubation times post-inoculation depend upon the expression level of boPrP(C) and the amount of prions in the inoculum. In the absence of clinical signs, pathognomonic markers of disease could be detected as early as 150 or 196 days post-inoculation by IHC and Western blot analysis, respectively. This result indicates that prion infectivity in experimental mouse bioassays can be measured earlier by assessing immunologically the presence of PrPres in brains from inoculated animals. Although these transgenic mice were also susceptible to sheep scrapie prion infection, the extent of incubation times was considerably longer and PrPres was detected in only 70% of inoculated mice. Interestingly, transgenic mice-propagated sheep scrapie prions displayed distinct biochemical properties when compared to both the original sheep scrapie and transgenic mouse-propagated BSE inoculum.