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白细胞介素-3转基因小鼠发生运动神经元变性,伴有针对脊髓运动神经元的自身免疫反应。

Transgenic mice for interleukin 3 develop motor neuron degeneration associated with autoimmune reaction against spinal cord motor neurons.

作者信息

Chavany C, Vicario-Abejón C, Miller G, Jendoubi M

机构信息

Genetics and Molecular Immunology Section, Laboratory of Immunology/National Eye Institute, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda MD 20892, USA.

出版信息

Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11354-9. doi: 10.1073/pnas.95.19.11354.

Abstract

Interleukin 3 (IL-3) stimulates the proliferation and differentiation of various haematopoietic progenitor cells. Recently, IL-3 and other cytokines were reported to exert a neurotrophic activity and to be associated with neurological disorders, suggesting their complex role in the central nervous system. We now show that overexpression of IL-3 in transgenic mice causes a motor neuron disease with several features of amyotrophic lateral sclerosis and progressive muscular atrophy. These animals exhibit hind limb paralysis at 7 months of age, associated with dendritic and axonal degeneration, loss of motor neurons in the spinal cord, and autoimmune reaction against these cells. We examined the effect of IL-3 on embryonic motor neurons survival in mixed spinal cord cultures. Our results suggest that motor neuronal degeneration is not directly triggered by the high level of expression of IL-3.

摘要

白细胞介素3(IL-3)可刺激各种造血祖细胞的增殖和分化。最近,有报道称IL-3和其他细胞因子具有神经营养活性,并与神经疾病有关,这表明它们在中枢神经系统中发挥着复杂的作用。我们现在发现,转基因小鼠中IL-3的过表达会导致一种运动神经元疾病,具有肌萎缩侧索硬化症和进行性肌肉萎缩的若干特征。这些动物在7个月大时出现后肢麻痹,伴有树突和轴突退化、脊髓运动神经元丧失以及针对这些细胞的自身免疫反应。我们研究了IL-3对混合脊髓培养物中胚胎运动神经元存活的影响。我们的结果表明,运动神经元的退化并非由IL-3的高水平表达直接引发。

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本文引用的文献

1
The role of cytokines in haematopoiesis.细胞因子在造血过程中的作用。
Eur J Haematol Suppl. 1996;60:69-74. doi: 10.1111/j.1600-0609.1996.tb01649.x.
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Review: cytokines and the pathogenesis of multiple sclerosis.综述:细胞因子与多发性硬化症的发病机制
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Rat microglial interleukin-3.大鼠小胶质细胞白细胞介素-3
J Neuroimmunol. 1994 Mar;50(2):203-14. doi: 10.1016/0165-5728(94)90047-7.

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