PLP1相关性疾病是PLP1基因突变导致的中枢神经系统髓鞘形成障碍性疾病，特征为基因型与临床表型存在明显相关性，为阐明发生机制拟进行： 1）在人类少突胶质细胞系MO13.3中进行PLP1过表达、敲低与突变体转染，观察mRNA与蛋白表达、内质网共定位、细胞凋亡和细胞活性改变阐明PLP1突变对少突胶质细胞功能的影响；2）PLP1基因过表达、敲除与点突变的转基因小鼠皮层脑组织进行髓鞘形态学、电生理特性与行为的改变阐明PLP1突变对少突胶质细胞功能与髓鞘形成的影响；3）构建16-17天胎龄皮层神经元-胶质细胞混合培养模型以研究体外培养细胞中髓鞘形成影响，转染PLP1过表达、敲低与突变体在细胞水平进行上述实验。旨在了解PLP1基因不同突变类型所致少突胶质细胞功能及髓鞘形成障碍可能的细胞与分子机制，深入理解PLP1相关性疾病复杂基因型与表型的相互关系，以期为这组疾病及类似疾病共同发生机制提供线索资料。

PLP1-related disorders is a hereditary disease due to abnormal myelin formation disease in central nervous system resulting from a deficiency of PLP1 gene. Prominenet genotype-phenotype correlation is revealed in this disorder. Studies will be performed to elucidate the pathogenesis of this disorder: 1) To explor the effects of different PLP1 mutations on oligdendrocytic function, alterations of PLP1 mRNA and protein expression, colocalization in the endoplasmic reticulum(ER), apoptosis and MTT will be measured in oligodendrocytes after constructed 9 PLP1 mutants and transfected them to MO13.3 human oligodendrocytes line; 2) In vivo study of PLP1 mutations on effects of oligodendrocytic function and myelin formation: changes of myelin morphometre, electrophysiology and behavior were used in mouse models with PLP1 overexpression, knockout and point mutaion; 3) An in vitro model for the study of myelin formation by neuron-glia co-culture will be constructed and used for testing above experimental contents by transfecting different PLP1 mutants in cellular and molecular level. The objective of this study is to demonstrate possible cellular and molecular mechanisms on effects of oligodendrocytic function and myelin formation resulting from PLP1 gene mutations and understanding complex genotype-phenotype correlation comprehensively.　 The results of this study might provide useful information of general mechanisms and pathogenesis for PLP1-related disorders and similar diseases.