Suzuki K, Suzuki K
Department of Neurology, University of North Carolina School of Medicine, Chapel Hill 27599, USA.
Brain Pathol. 1995 Jul;5(3):249-58. doi: 10.1111/j.1750-3639.1995.tb00601.x.
The twitcher is a naturally-occurring mouse mutant caused by an abnormality in the gene coded for galactosylceramidase. It is therefore genetically equivalent to human globoid cell leukodystrophy (Krabbe disease). Affected mice develop clinical symptoms at the onset of the active myelination period and, if untreated, die by 35 +/- days. The pathology is very similar to that in human disease. Toxicity of galactosylsphingosine (psychosine) that accumulates abnormally in the nervous system is considered to be primarily responsible for the pathogenesis. Transplantation of bone marrow cells from normal donors is partially effective and triples the life span of affected mice to 100 +/- days with evidence of remyelination in the CNS. The mutation responsible for the twitcher mutant has recently been identified. It is expected that this model will be useful for basic studies on treatment of this group of genetic disorders affecting the brain through transgenic and/or gene therapy approaches.
震颤鼠是一种自然发生的小鼠突变体，由编码半乳糖神经酰胺酶的基因异常引起。因此，它在基因上等同于人类球状细胞脑白质营养不良症（克拉伯病）。受影响的小鼠在活跃髓鞘形成期开始时出现临床症状，若不治疗，会在35±天内死亡。其病理学与人类疾病非常相似。在神经系统中异常积累的半乳糖神经鞘氨醇（半乳糖神经酰胺）的毒性被认为是发病机制的主要原因。来自正常供体的骨髓细胞移植有部分效果，可使受影响小鼠的寿命延长两倍，达到100±天，且中枢神经系统有髓鞘再生的迹象。导致震颤鼠突变的基因最近已被确定。预计该模型将有助于通过转基因和/或基因治疗方法对这组影响大脑的遗传疾病进行基础研究。
