Motor behavioral and neuropathological deficits in mice deficient for normal prion protein expression.
Motor behavioral and neuropathological deficits in mice deficient for normal prion protein expression.
复制标题
缺乏正常朊病毒蛋白表达的小鼠的运动行为和神经病理学缺陷。
DOI：
10.1016/j.bbadis.2007.04.004
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Telling,GlennC
中科院分区：
文献类型：
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作者：
Nazor,KarahE;Seward,Tanya;Telling,GlennC
缺乏朊病毒蛋白（PrP）的小鼠（称为Prnp 0/0小鼠）没有病理学和明显正常的行为，与朊病毒发病机制有关，涉及PrPC介导的神经保护作用的进行性丧失，这是很难调和的。然而，在这里，我们报告说，Prnp 0/0小鼠表现出显着的年龄相关的缺陷，在运动协调和平衡与小鼠相比，表达野生型Prnp的同基因背景，行为受损的Prnp 0/0小鼠的大脑显示海绵状病理和反应性星形胶质细胞增生，通常伴随朊病毒疾病的主要神经病理学标志。与Gerstmann-Sträussler-Scheinker综合征（GSS）患者出现小脑共济失调作为早期症状一致，GSS是一种遗传性人类朊病毒疾病，GSS转基因（Tg）小鼠模型中表现出的运动协调和平衡缺陷明显早于终末期神经退行性疾病的发作。我们的研究结果是一致的机制，其中正常的PrPC功能的损失是一个重要的病理组成部分朊病毒疾病。
It has been difficult to reconcile the absence of pathology and apparently normal behavior of mice lacking prion protein (PrP), referred to as Prnp0/0mice, with a mechanism of prion pathogenesis involving progressive loss of PrPC-mediated neuroprotection. However, here we report that Prnp0/0mice exhibit significant age-related defects in motor coordination and balance compared with mice expressing wild type Prnp on a syngeneic background, and that the brains of behaviorally-impaired Prnp0/0mice display the cardinal neuropathological hallmarks of spongiform pathology and reactive astrocytic gliosis that normally accompany prion disease. Consistent with the appearance of cerebellar ataxia as an early symptom in patients with Gerstmann–Sträussler–Scheinker syndrome (GSS), an inherited form of human prion disease, motor coordination and balance defects manifested in a transgenic (Tg) mouse model of GSS considerably earlier than the onset of end-stage neurodegenerative disease. Our results are consistent with a mechanism in which loss of normal PrPCfunction is an important pathological component of prion diseases.