Peripheral circulation of the prion infectious agent in transgenic mice expressing the ovine prion protein gene in neurons only
Peripheral circulation of the prion infectious agent in transgenic mice expressing the ovine prion protein gene in neurons only
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DOI：
10.1086/512085
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发表时间：
2007-04-01
影响因子：
6.4
通讯作者：
Bencsik, Anna
中科院分区：
文献类型：
--
作者：
Crozet, Carole;Lezmi, Stephane;Bencsik, Anna
背景。对于朊病毒疾病，即使大量证据表明淋巴网状系统（LRS）和周围神经都参与瘙痒病神经侵袭，但朊病毒侵入中枢神经系统的过程仍只被部分了解。转基因Tg（OvPrP4）小鼠在大鼠神经元特异性烯醇化酶启动子下表达羊朊病毒蛋白（PrP）基因，用于研究通过脑内（ic）和腹膜内（ip）途径接种瘙痒病朊病毒后的朊病毒脑外循环。令人惊讶的是，在接种朊病毒的小鼠的脾脏中检测到了 PrPSc。此外，外周非神经组织中羊 PrPC 的缺失并不能阻止腹膜内攻击后的神经侵袭。此外，在接种 ic 朊病毒之前接受脾切除术的 Tg(OvPrP4) 小鼠中进行的初步研究表明，该疾病的病程被延迟。结论。鉴于这些小鼠在神经元细胞中表达羊 PrP 基因，但在非神经组织中不表达，我们的结果表明，LRS 细胞表达的 PrPC 对于神经侵袭或其积累 PrPSc 的能力不是必需的，并强调了 PrPC 或 PrPSc 的脑外循环对于疾病发展的重要性。
Background. For prion diseases, even if a large body of evidence indicates that both the lymphoreticular system (LRS) and peripheral nerves are involved in scrapie neuroinvasion, the processes by which prions invade the central nervous system are only partially understood.Methods. Transgenic Tg(OvPrP4) mice, which express the ovine prion protein (PrP) gene under the rat neuron specific enolase promoter on a knockout background, were used to study prion extracerebral circulation after scrapie prions were inoculated via the intracerebral (ic) and the intraperitoneal (ip) route.Results. Surprisingly, PrPSc was detected in the spleens of mice inoculated ic with prions. Moreover, the absence of the ovine PrPC in nonneural tissue at the periphery did not stop neuroinvasion after ip challenge. Additionally, pilot studies performed in Tg(OvPrP4) mice that had undergone splenectomy before ic prion inoculation showed that the time course of the disease is delayed.Conclusions. Given that these mice express the ovine PrP gene in neuronal cells but not in nonnervous tissue, our results suggest that PrPC expressed by cells of the LRS are not necessary for neuroinvasion or for their ability to accumulate PrPSc and emphasize the importance of extracerebral circulation of PrPC or PrPSc for the development of the disease.