INCREASED EXPRESSION OF NEUROFILAMENT SUBUNIT-NF-L PRODUCES MORPHOLOGICAL ALTERATIONS THAT RESEMBLE THE PATHOLOGY OF HUMAN MOTOR-NEURON DISEASE
INCREASED EXPRESSION OF NEUROFILAMENT SUBUNIT-NF-L PRODUCES MORPHOLOGICAL ALTERATIONS THAT RESEMBLE THE PATHOLOGY OF HUMAN MOTOR-NEURON DISEASE
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DOI：
10.1016/0092-8674(93)90157-l
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发表时间：
1993-04-09
期刊：
影响因子：
64.5
通讯作者：
CLEVELAND, DW
中科院分区：
文献类型：
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作者：
XU, ZS;CORK, LC;CLEVELAND, DW
运动神经元细胞体和近端轴突神经丝的过度积累是许多人类运动神经元疾病早期的主要病理标志。为了直接测试主要神经丝亚基NF-L过表达的后果，我们生产了转基因小鼠，使其在坐骨神经中积累NF-L约为正常水平的4倍。在幼龄动物中，脊髓前角的运动神经元有大量的神经丝堆积，核周肿胀，核偏心定位。NF-L积累伴随着轴突变性、近端轴突肿胀和严重的骨骼肌萎缩的频率增加。这些数据表明，运动神经元中神经丝的广泛积累可以触发神经退行性过程。
Excessive accumulation of neurofilaments in the cell bodies and proximal axons of motor neurons is a major pathological hallmark during the early stages of many human motor neuron diseases. To test directly the consequence of overexpression of the major neurofilament subunit NF-L, we produced transgenic mice that accumulate NF-L to approximately 4-fold the normal level in the sciatic nerve. In young animals, the motor neurons of the ventral horn of the spinal cord have massive accumulations of neurofilaments, swollen perikarya, and eccentrically localized nuclei. NF-L accumulation is accompanied by an increased frequency of axonal degeneration, proximal axon swelling, and severe skeletal muscle atrophy. These data indicate that extensive accumulation of neurofilaments in motor neurons can trigger the neurodegenerative process.