Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA.
Neurobiol Dis. 2011 Nov;44(2):231-8. doi: 10.1016/j.nbd.2011.07.007. Epub 2011 Jul 18.
Pelizaeus-Merzbacher disease (PMD) most frequently results from duplication of the Plp1 gene with a correlation between disease severity and increasing copy number of the gene. Animal models of PMD, in particular those overexpressing the Plp1 gene, have been sought in attempts to provide systems in which potential therapies can be tested. Here we describe a rat model of the severe connatal form of PMD and provide a detailed characterization of its pathology and molecular biology, prior to testing therapeutic approaches. We determined the exact copy number of Plp1, and the resulting effects on RNA and protein expression. Distinct differences in myelin and disparate distributions of myelin protein markers in comparison to wild-type controls were observed. Altered expression of Plp1 also caused an increase in the apoptotic cell death of oligodendrocytes. These results provide the platform from which to test the effectiveness of in vivo therapies.
佩利兹-梅布克病（PMD）最常因 Plp1 基因的重复而导致，其疾病严重程度与基因拷贝数的增加呈正相关。PMD 的动物模型，特别是那些过度表达 Plp1 基因的动物模型，一直是人们试图提供潜在治疗方法测试系统的研究对象。本文描述了一种严重先天性 PMD 的大鼠模型，并对其病理学和分子生物学进行了详细的特征描述，之后对治疗方法进行了测试。我们确定了 Plp1 的精确拷贝数，以及其对 RNA 和蛋白质表达的影响。与野生型对照相比，髓鞘和髓鞘蛋白标志物的分布存在明显差异。Plp1 的异常表达还导致少突胶质细胞的凋亡细胞死亡增加。这些结果为体内治疗的有效性测试提供了平台。
