Molecular Pathology of the dysmyelinating diseases and generation of the model animals

髓鞘形成障碍疾病的分子病理学及模型动物的产生

• 批准号: 06680741
• 负责人: IWAKI Akiko
• 金额: $ 1.47万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06680741/
• 关键词: dysmyelination; myelin; PLP; ミエリン形成不全症; プロテオリピド蛋白質

Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder of the central nervous system, characterized by an early onset of nystagmus and spastic quadriplegia (motor developmental delay). It is usually fatal in infancy or childhood. In this study we analyzed the myelin proteolipid protein (PLP) gene of the 26 PMD families by PCR-SSCP followed by direct sequencing of the PCR products and then found seven novel mutations including three missense, one nonsense, one flame-shift, and two splice mutations in the PLP genes. One of the families includes 3 males who have manifestations of the juvenile form of PMD with spastic paraplegia caused by a splice mutation. There was no mutation in the exons of the PLP genes of the remaining 19 PMD families. Further analysis of the causes of the disease in those PMD families are now under investigations. To know the relationship of phenotype of PMD with the mutation and the function of PLP,we established a system for expression of the exogenous PLP/DM20 gene in cultured cells before trying to make a mouse model for PMD.We obtained C6 cells expressing DM20 under the control of the MMTV promoter and prepared antibodies against DM20-peptides to investigate the intracellular localization of DM20. Characterzation of those cells are proceeded.

Pelizaeus-Merzbacher疾病（PMD）是中枢神经系统的X连锁障碍性疾病，其特征在于眼球震颤和痉挛性四肢瘫痪（运动发育延迟）的早期发作。通常在婴儿期或童年时致命。在这项研究中，我们通过PCR-SSCP分析了26 pmd家族的髓磷脂蛋白蛋白蛋白（PLP）基因，然后直接对PCR产物进行测序，然后发现了七个新型突变，包括三个失误，一个废话，一个火焰转移和两个PLP基因中的剪接突变。其中一个家庭包括3名男性，这些雄性具有少年形式的PMD，并由剪接突变引起的痉挛性截瘫。其余19个PMD家族的PLP基因的外显子没有突变。现在正在研究这些PMD家族中该疾病原因的进一步分析。为了了解PMD的表型与PLP的突变和功能的关系，我们在试图制作PMD的小鼠模型之前，建立了一个用于表达外源PLP/DM20基因的系统。 MMTV启动子和针对DM20肽的抗体的控制，以研究DM20的细胞内定位。进行这些细胞的特征。

项目成果

Akiko Iwaki: "Pelizaeous-Merzbacher disease" Clinical Neuroscience. 13. 1320-1322 (1995)

Akiko Iwaki：“Pelizaeous-Merzbacher 病”临床神经科学。

岩城明子: "Pelizaeus-Merzbacher病" Clinical Neuroscience. 13. 1320-1322 (1995)

Akiko Iwaki：“Pelizaeus-Merzbacher 病”临床神经科学 13. 1320-1322 (1995)。