THE MAJOR MYELIN GLYCOPROTEIN

主要的髓磷脂糖蛋白

• 批准号: 3078282
• 负责人: JAMES SALZER
• 金额: $ 4.4万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3078282
• 关键词: complementary DNA; electron microscopy; gel electrophoresis; gene expression; genetic library; genetic manipulation; genetic regulation; genetic transcription; membrane structure; messenger RNA; molecular cloning; myelin; myelination; myelinopathy; neurophysiology; nucleic acid sequence; structural genes; tissue /cell culture

Long term objectives of this project are to characterize early events of myelinogenesis and to gain an understanding of the process by which the expression of genes for specific myelin proteins is regulated. To this end, the genes for the major peripheral myelin glycoproteins, Po and the myelin associated glycoprotein (MAG), will be studied. Po is an integral membrane protein and is the major peripheral myelin protein; it is likely to play and important role in the structural integrity of the peripheral myelin sheath. MAG has a localization within the myelin sheath that suggests a role in mediating glial-neuronal interactions; it is also preferentially lost in acute plaques of multiple sclerosis and it is the antigenic target of paraprotein induced peripheral neuropathies further underscoring its potential importance. cDNA clones for MAG and Po will be isolated by a common strategy. Antibodies against purified MAG and Po will be used to identify, in vitro translation experiments, mRNA fractions extracted from mouse peripheral nerves, which are enriched in sequences coding for MAG and Po. These fractions will be used as probes to isolate the respective cDNAs from a mouse peripheral nerve library (to be prepared). The primary structure of the proteins will be derived from the nucleotide sequence of the MAG and Po cDNAs which will also be used to isolate the genes for Po and MAG from a genomic library. The elucidation of the structure of the genes and an evaluation of intra-exon relationships may be useful in identifying possible functional domains of the proteins. Electron microscopic heteroduplex analysis of Po and PLP may reveal common sequences reflecting a common evolutionary origin. The defect in the peripheral dysmyelinating mouse mutatn Trembler, will be studied by determining mRNA levels of MAG, Po and the MBPs. Long range goals include studying the regulation of myelin protein gene expression in a peripheral myelin tissue culture system.

该项目的长期目标是描述 髓鞘形成，并获得了解的过程中， 特定髓鞘蛋白基因的表达受到调节。 本 最后，主要的外周髓鞘糖蛋白，Po和 髓鞘相关糖蛋白（MAG），将进行研究。 Po是一个积分 膜蛋白，是主要的外周髓鞘蛋白;它可能是 在外围的结构完整性中发挥重要作用 髓鞘 MAG在髓鞘内定位， 表明在介导神经胶质-神经元相互作用中的作用;它也是 在多发性硬化的急性斑块中优先丢失， 副蛋白诱导的周围神经病变的抗原靶点还 强调其潜在的重要性。 MAG和Po的cDNA克隆将被克隆。 被一个共同的战略所孤立。 针对纯化的MAG和Po的抗体将 可用于鉴定，在体外翻译实验中，mRNA片段 从小鼠外周神经中提取，其富含序列 MAG和Po的编码。 这些馏分将用作探针，以分离 将来自小鼠外周神经文库（待 准备）。 蛋白质的一级结构将源自 MAG和Po cDNA的核苷酸序列，其也将用于 从基因组文库中分离Po和MAG的基因。 阐明 基因的结构和外显子间关系的评估 可能有助于识别蛋白质可能的功能结构域。 电子显微镜异源双链分析Po和PLP可能揭示共同的 序列反映了共同的进化起源。 中的缺陷 外周髓鞘形成障碍小鼠突变体Trembler，将通过 测定MAG、Po和MBP的mRNA水平。 长期目标包括 研究外周血中髓鞘蛋白基因表达的调控， 髓鞘组织培养系统