Andersen Julie
Buck Institute, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Sci Aging Knowledge Environ. 2003 May 7;2003(18):PE10. doi: 10.1126/sageke.2003.18.pe10.
Although the causative genetic mutations for a subset of some of the most prevalent human motor neurodegenerative diseases have been identified, the exact molecular mechanisms behind motor neuron and associated muscular loss in these disorders remain an unsolved mystery. In a recent issue of Science, two mutagenesis-derived mouse mutants are described that contain missense mutations in the gene encoding the cytoplasmic dynein heavy-chain protein, which is part of a major cellular motor complex involved in retrograde axonal transport. These mutations result in progressive motor neuron degeneration in heterozygous animals and Lewy-like inclusion bodies in the homozygotes resembling those that occur in related human pathologies such as amyotrophic lateral sclerosis, spinal muscular atrophy, and spinal-bulbar muscular atrophy. This discovery opens up the exciting possibility that similar mutations may be involved in these human disease states.
尽管已经确定了一些最常见的人类运动神经元退行性疾病的部分致病基因突变，但这些疾病中运动神经元和相关肌肉损失背后的确切分子机制仍是未解之谜。在最近一期的《科学》杂志上，描述了两个诱变产生的小鼠突变体，它们在编码细胞质动力蛋白重链蛋白的基因中含有错义突变，该蛋白是参与逆行轴突运输的主要细胞运动复合体的一部分。这些突变导致杂合子动物中运动神经元进行性退化，纯合子中出现类似路易小体的包涵体，类似于在相关人类疾病如肌萎缩侧索硬化症、脊髓性肌萎缩症和延髓脊髓性肌萎缩症中出现的情况。这一发现开启了令人兴奋的可能性，即类似的突变可能与这些人类疾病状态有关。
