Characterization and molecular investigation of pathogenesis in a novel model of human familial ALS.

肌萎缩侧索硬化症(ALS，又称运动神经元病)由于大脑和脊髓中运动神经细胞的退化而导致进行性瘫痪。人们失去了移动肢体、进食或说话的能力，并死于呼吸困难，通常在症状出现后3年内。这种疾病没有有效的治疗方法。当有缺陷的基因代代相传时，肌萎缩侧索硬化症可能发生在一个人或家庭内部。这些家族性形式没有临床特征区别于其他类型。SOD1是最常见的参与基因，对SOD1缺陷的研究为了解ALS的发病机制和确定治疗靶点提供了机会。这项研究项目的目的是研究一种新的小鼠模型，它携带与一组ALS患者完全相同的基因缺陷。我们将描述小鼠的疾病发展过程，因此我们将利用小鼠来分析疾病早期运动神经细胞的疾病机制。发现潜在的疾病机制是确定临床试验药物靶点的基础，小鼠也可能被用作测试新疗法的疾病模型。

Amyotrophic lateral sclerosis, (ALS, also called Motor neurone disease) causes progressive paralysis due to the degeneration of motor nerve cells in the brain and spinal cord. People lose the ability to move their limbs, eat or speak and die from breathlessness, usually within 3 years of symptom onset. There is no effective treatment for the disease. ALS can occur in one individual or within families when a defective gene is passed down through the generations. No clinical characteristic differentiates the familial forms from the others. SOD1 is the most frequently involved gene and the study of SOD1 defects is an opportunity for understanding ALS disease mechanisms and to identify therapeutic targets. The purpose of this research project is to study a new mouse model which carries the exact same genetic defect as a group of ALS patients. We will characterize the disease progression in the mice and so we will use the mice to analyze the disease mechanisms in the motor nerve cells in the very early stages of disease. The discovery of underlying disease mechanisms is fundamental to the identifying drug targets for clinical trials, and the mice may also be used as a disease model to test new therapies.