关键词: PrP protein PrPSc classical scrapie protease resistant prion strain typing transgenic mice

Mesh : Mice Animals Cattle Sheep Prions / metabolism Scrapie / metabolism Prion Proteins / genetics PrPSc Proteins / metabolism Mice, Transgenic

来  源:   DOI:10.1111/nan.12963

Abstract:
OBJECTIVE: CH1641 was discovered in 1970 as a scrapie isolate that was unlike all other classical strains of scrapie isolated so far. We performed bio-assays of CH1641 in mice in order to further characterise this specific isolate.
METHODS: We inoculated the original CH1641 isolate into ovine and bovine prion protein (PrP) transgenic mice as well as wild-type mice. In addition, we performed cross- and back passages between the various mouse lines to examine if one identical prion strain was isolated in all mouse lines or whether multiple prion strains exist in CH1641.
RESULTS: We report the first successful transmission of CH1641 to wild-type RIII mice and via RIII mice to wild-type VM mice. Unexpectedly, analysis of the protease-resistant prion protein (PrPres ) in wild-type mice showed a classical scrapie banding pattern differing from the banding pattern of the original CH1641 isolate. Cross- and back passages of CH1641 between the various mouse lines confirmed that the same prion strain had been isolated in all mouse lines.
CONCLUSIONS: The CH1641 isolate consists of a single prion strain but its molecular banding pattern of PrPres differs between wild-type mice and PrP transgenic mice. Consequently, molecular banding patterns of PrPres should be used with caution in strain typing since they do not solely depend on the properties of the prion strain but also on the host prion protein.
摘要:
目的:CH1641于1970年被发现为瘙痒病分离株,与迄今为止分离的所有其他经典瘙痒病菌株不同。我们在小鼠中进行了CH1641的生物测定以进一步表征该特定分离株。
方法:我们将原始CH1641分离物接种到绵羊和牛朊病毒蛋白(PrP)转基因小鼠以及野生型小鼠中。此外,我们在不同小鼠品系之间进行交叉传代和反向传代,以检查是否在所有小鼠品系中分离出一个相同的朊病毒株,或者CH1641中是否存在多个朊病毒株.
结果:我们报道了CH1641首次成功传播至野生型RIII小鼠,并通过RIII小鼠成功传播至野生型VM小鼠。出乎意料的是,在野生型小鼠中对蛋白酶抗性朊病毒蛋白(PrPres)的分析表明,经典的瘙痒病条带模式与原始CH1641分离株的条带模式不同。CH1641在各种小鼠品系之间的交叉和反向传代证实了在所有小鼠品系中已分离出相同的朊病毒品系。
结论:CH1641分离株由单个朊病毒株组成,但其PrPres的分子条带模式在野生型小鼠和PrP转基因小鼠之间有所不同。因此,在菌株分型中应谨慎使用PrPres的分子条带模式,因为它们不仅取决于pr病毒菌株的特性,而且还取决于宿主pr病毒蛋白。
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