NEUROLOGIC DISEASE INDUCED IN TRANSGENIC MICE BY CEREBRAL OVEREXPRESSION OF INTERLEUKIN-6
NEUROLOGIC DISEASE INDUCED IN TRANSGENIC MICE BY CEREBRAL OVEREXPRESSION OF INTERLEUKIN-6
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DOI：
10.1073/pnas.90.21.10061
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发表时间：
1993-11-01
影响因子：
11.1
通讯作者：
MUCKE, L
中科院分区：
文献类型：
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作者：
CAMPBELL, IL;ABRAHAM, CR;MUCKE, L
细胞因子被认为是影响中枢神经系统（CNS）的生理和病理生理过程中的重要介质。为了探索这一假设，产生了转基因小鼠，其中细胞因子白细胞介素6（IL-6），在神经胶质细胞酸性蛋白基因启动子的调控控制下，在中枢神经系统中过表达。许多转基因创始小鼠及其后代表现出神经系统综合征，其严重程度与脑IL-6表达水平相关。具有高水平IL-6表达的转基因小鼠发展为严重的神经系统疾病，其特征为奔跑、震颤、共济失调和癫痫发作。神经病理学表现包括神经变性、星形细胞增多、血管生成和诱导急性期蛋白产生。这些发现表明，细胞因子如IL-6可在炎症性、感染性和神经退行性CNS疾病中具有直接致病作用。
Cytokines are thought to be important mediators in physiologic and pathophysiologic processes affecting the central nervous system (CNS). To explore this hypothesis, transgenic mice were generated in which the cytokine interleukin 6 (IL-6), under the regulatory control of the glial fibrillary acidic protein gene promoter, was overexpressed in the CNS. A number of transgenic founder mice and their offspring exhibited a neurologic syndrome the severity of which correlated with the levels of cerebral IL-6 expression. Transgenic mice with high levels of IL-6 expression developed severe neurologic disease characterized by runting, tremor, ataxia, and seizure. Neuropathologic manifestations included neuro-degeneration, astrocytosis, angiogenesis, and induction of acute-phase-protein production. These findings indicate that cytokines such as IL-6 can have a direct pathogenic role in inflammatory, infectious, and neurodegenerative CNS diseases.