FUNCTIONAL DOMAINS OF THE MYELIN BASIC PROTEINS

完全了解髓鞘碱性蛋白(MBPS)所起的作用 将阐明髓鞘膜形成的重要机制 潜在的髓鞘修复。一种髓鞘功能障碍突变体的可用性 颤抖的老鼠提供了一个独特的机会来研究这一贡献 这一组蛋白质对髓鞘膜形成的影响，因为 寒战缺乏功能性的MBP基因，无法正常生成 致密的中枢神经系统髓鞘。这个提议的目的是1)构建 包含将插入的全长和截短Mbps的cDNA 转化成在啮齿动物细胞中高效表达的载体，2)评估 变长MBPS与寒战单层髓鞘膜的结合 3)载体导入寒战少突胶质细胞 包含那些已被证明与膜结合的MBP结构 水泡。最终目标是将这些转基因细胞移植到 同源基因寒战小鼠获得重新髓鞘形成。分子和细胞 将使用生物技术以及免疫细胞化学在 光镜和电子显微镜水平。 脱髓鞘在许多人导致的残疾中起着重要作用 神经系统疾病，无论是像多发性硬化症那样主要影响髓鞘，还是 其次是中风和创伤。彻底的、批判性的检查 Mbps在髓鞘形成和稳定中的作用 膜有望阐明促进细胞生长的机制 对正常神经功能至关重要的膜的再生。

A complete understanding of the role the myelin basic proteins (MBPs) play in organizing the myelin membrane will elucidate important mechanisms underlying myelin repair. The availability of a dysmyelinating mutant mouse, the shiverer, affords a unique opportunity to study the contribution of this single set of proteins to myelin membrane formation, since the shiverer lacks a functional MBP gene and is unable to generate normally compacted CNS myelin. This proposal aims to 1) construct plasmids containing cDNAs of full length and truncated MBPs which will be inserted into vectors that are efficiently expressed in rodent cells, 2) evaluate binding of the varying-length MBPs to shiverer unilamellar myelin membrane vesicles, and 3) transfect shiverer oligodendrocytes with vectors containing those MBP constructs that have been shown to bind to membrane vesicles. The eventual goal is to transplant these transfected cells into syngenic shiverer mice to obtain remyelination. Molecular and cellular biological techniques will be used as well as immunocytochemistry at the light and electron microscopic level. Demyelination plays a significant role in the disability caused by many neurological diseases, whether they affect myelin primarily as in MS, or secondarily as in stroke and trauma. A thorough and critical examination of the role the MBPs play in the formation and stabilization of the myelin membrane will hopefully elucidate mechanisms that encourage the regeneration of a membrane so vital to normal neurologic function.