THE MAJOR MYELIN GLYCOPROTEIN

该项目的长期目标是描述早期事件的特征 并了解髓鞘形成的过程。 特定髓鞘蛋白的基因表达受到调控。对这件事 最后，主要外周髓鞘糖蛋白的基因Po和 髓鞘相关糖蛋白(MAG)，将被研究。Po是一个积分 膜蛋白，是主要的外周髓鞘蛋白；它很可能 在外围设备的结构完整性中发挥重要作用 髓鞘。MAG在髓鞘内有一个定位 暗示了在调节神经胶质细胞-神经元相互作用中的作用；它也是 优先消失在多发性硬化症的急性斑块中，它是 副蛋白抗原靶向进一步诱导周围神经病变 强调其潜在的重要性。MAG和Po的cDNA克隆将是 被共同的战略所孤立。抗纯化MAG和Po Will的抗体 用于在体外翻译实验中鉴定信使核糖核酸组分 从富含序列的小鼠周围神经中提取 MAG和PO的编码。这些组分将被用作探针来分离 来自小鼠周围神经文库的各自的cDNA(将被 准备好了)。蛋白质的一级结构将来自于 MAG和Po cDNA的核苷酸序列也将用于 从基因组文库中分离Po和MAG基因。《解释》 基因的结构和外显子内关系的评估 可能有助于确定蛋白质的可能功能结构域。 Po和PLP的电子显微镜异源双链分析可能揭示共同的 反映共同进化起源的序列。它的缺陷就是 外周髓鞘脱髓鞘障碍小鼠突变颤抖，将通过 测定MAG、Po和MBPS的mRNA水平。长期目标包括 外周血髓鞘蛋白基因表达调控的研究 髓鞘组织培养体系。

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.