MICE DEVOID OF THE GLIAL FIBRILLARY ACIDIC PROTEIN DEVELOP NORMALLY AND ARE SUSCEPTIBLE TO SCRAPIE PRIONS
MICE DEVOID OF THE GLIAL FIBRILLARY ACIDIC PROTEIN DEVELOP NORMALLY AND ARE SUSCEPTIBLE TO SCRAPIE PRIONS
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DOI：
10.1016/0896-6273(95)90238-4
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发表时间：
1995-01-01
期刊：
影响因子：
16.2
通讯作者：
ITOHARA, S
中科院分区：
文献类型：
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作者：
GOMI, H;YOKOYAMA, T;ITOHARA, S
胶质细胞酸性蛋白（GFAP）是中枢神经系统星形胶质细胞特异性表达的一种中间丝蛋白。为了检查GFAP在体内的功能，通过在胚胎干细胞中的基因靶向破坏GFAP基因。突变纯合子小鼠完全没有GFAP，但表现出正常的发育，并显示在中枢神经系统没有明显的解剖异常。当接种传染性羊瘙痒症朊病毒时，突变小鼠表现出朊病毒疾病的典型神经病理学变化。感染性朊病毒在突变小鼠大脑中的积累程度与对照组小鼠相似。这些结果表明，GFAP是不是必不可少的CNS的形态发生或星形胶质细胞对神经元损伤的反应。这些结果反驳了GFAP在朊病毒疾病的发病机制中起关键作用的假设。
Glial fibrillary acidic protein (GFAP) is an intermediate filament protein specifically expressed in astrocytes in the CNS. To examine the function of GFAP in vivo, the Gfap gene was disrupted by gene targeting in embryonic stem cells. Mice homozygous for the mutation were completely devoid of GFAP but exhibited normal development and showed no obvious anatomical abnormalities in the CNS. When inoculated with infectious scrapie prions, the mutant mice exhibited neuropathological changes typical of prion diseases. Infectious prions accumulated in brains of the mutant mice to a degree similar to that in control littermates. These results suggest that GFAP is not essential for the morphogenesis of the CNS or for astrocytic responses against neuronal injury. The results argue against the hypothesis that GFAP plays a crucial role in the pathogenesis of prion diseases.