Disease progression of human SOD1 (G93A) transgenic ALS model rats
Disease progression of human SOD1 (G93A) transgenic ALS model rats
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DOI：
10.1002/jnr.20708
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发表时间：
2006-01-01
影响因子：
4.2
通讯作者：
Okano, H
中科院分区：
文献类型：
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作者：
Matsumoto, A;Okada, Y;Okano, H
最近开发的肌萎缩侧索硬化症（ALS）大鼠模型（其中大鼠携带突变的人SOD 1（G93 A）基因）极大地扩展了潜在实验的范围，因为大鼠的大尺寸允许生化分析和治疗试验，例如鞘内注射新药和干细胞移植。这种疾病模型的确切性质仍不清楚。我们描述了三种疾病表型：前肢型、后肢型和全身型。通过体重、斜面试验、笼内活动、自动运动分析系统（SCANET）、翻正反射等建立了一个简单、无创、客观的评价系统。此外，我们创建了一个新的量表，运动评分，它可以用于任何表型，不需要特殊的仪器。通过这些方法，我们统一和定量评估了发病，进展和疾病持续时间，并清楚地显示了该模型的可变临床过程;发病后的疾病进展在前肢型中比在后肢型中更具侵略性。更重要的是，由我们的评估系统定义的疾病阶段与脊髓运动神经元的损失相关性很好。特别是，肌肉无力的发作与大约50%的脊髓运动神经元的损失相吻合。这项研究应该为未来的实验提供一个有价值的工具，以测试潜在的ALS疗法。(c)2005 Wiley-Liss，Inc.
The recent development of a rat model of amyotrophic lateral sclerosis (ALS) in which the rats harbor a mutated human SOD1 (G93A) gene has greatly expanded the range of potential experiments, because the rats' large size permits biochemical analyses and therapeutic trials, such as the intrathecal injection of new drugs and stem cell transplantation. The precise nature of this disease model remains unclear. We described three disease phenotypes: the forelimb-, hindlimb-, and general-types. We also established a simple, non-invasive, and objective evaluation system using the body weight, inclined plane test, cage activity, automated motion analysis system (SCANET), and righting reflex. Moreover, we created a novel scale, the Motor score, which can be used with any phenotype and does not require special apparatuses. With these methods, we uniformly and quantitatively assessed the onset, progression, and disease duration, and clearly presented the variable clinical course of this model; disease progression after the onset was more aggressive in the forelimb-type than in the hindlimb-type. More importantly, the disease stages defined by our evaluation system correlated well with the loss of spinal motor neurons. In particular, the onset of muscle weakness coincided with the loss of approximately 50% of spinal motor neurons. This study should provide a valuable tool for future experiments to test potential ALS therapies. (c) 2005 Wiley-Liss, Inc.