Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis.
Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis.
复制标题
DOI：
--
复制
发表时间：
1994-12
期刊：
影响因子：
--
通讯作者：
M. C. Canto;M. Gurney
中科院分区：
文献类型：
--
作者：
M. C. Canto;M. Gurney
表达突变的Cu，Zn超氧化物歧化酶（SOD）的转基因小鼠，在93号位置含有甘氨酸被丙氨酸取代，发展为普遍影响运动神经元的疾病。光镜和超微结构检查显示，脊髓前角大神经元微囊化是其最早的病理特征。这些空泡起源于粗内质网的扩张和线粒体的退化。在疾病的晚期，微泡型让位给萎缩的前角，表现出严重的神经元消耗和一些存活神经元的透明丝状包涵体。后角神经元和背根神经节不受影响。随着疾病进展，前柱和侧柱的中度退变，前根的严重退变，后柱和根的轻度退变变得明显。这项研究表明，尽管SOD是一种普遍存在的酶，但已知在家族性肌萎缩性侧索硬化症患者中发生的SOD突变可能只影响选择性的神经元群。
Transgenic mice expressing mutant Cu,Zn superoxide dismutase (SOD), containing a substitution of glycine at position 93 by alanine, develop disease prevalently affecting motor neurons. Light microscopical and ultrastructural studies reveal that the earliest pathological features are microvesiculation of large neurons of the anterior horns of the spinal cord. These vacuoles originate from dilation of rough endoplasmic reticulum and from degenerating mitochondria. At the end stage of the disease, the microvesicular pattern gives way to atrophic anterior horns showing severe neuronal depletion and hyaline, filamentous inclusions in some of the surviving neurons. Posterior horn neurons and dorsal root ganglia are not affected. With disease progression, moderate degeneration of anterior and lateral columns, severe degeneration of anterior roots, and mild degeneration in posterior columns and roots become apparent. This study shows that a mutation in SOD, known to occur in a percentage of familial amyotrophic lateral sclerosis patients, may affect only selective neuronal populations, although SOD is a ubiquitous enzyme.