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

肌萎缩侧索硬化症（ALS，也称为运动神经元疾病）由于大脑和脊髓中的运动神经细胞的变性而导致进行性瘫痪。人们失去了移动四肢，进食或说话的能力，通常在症状发作后3年内死于呼吸困难。这种病没有有效的治疗方法。ALS可以发生在一个人或家庭内，当一个有缺陷的基因通过几代人传递。没有临床特征将家族型与其他型区分开来。SOD1是最常见的参与基因，SOD1缺陷的研究是了解ALS疾病机制和确定治疗靶点的机会。该研究项目的目的是研究一种新的小鼠模型，该模型携带与一组ALS患者完全相同的遗传缺陷。我们将描述小鼠的疾病进展，因此我们将使用小鼠来分析疾病早期阶段运动神经细胞中的疾病机制。发现潜在的疾病机制是确定临床试验药物靶点的基础，小鼠也可用作疾病模型来测试新疗法。

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.