FUNCTIONAL DOMAINS OF THE MYELIN BASIC PROTEINS

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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.