Recently, our conception of the two principal myelin protein genes, i.e. the myelin basic protein (MBP) and proteolipid protein (PLP) genes, has begun to change in view of new information about their structure, expression patterns and possible non-myelin related functions of their products. There is a considerable body of evidence to suggest that the PLP/DM20 gene plays roles other than that encoding the major myelin structural proteins in non-myelinating cells. This could occur either through multiple activities of the """"""""classic"""""""" PLP and DM20, or through the existence of other products of the gene that have not yet been identified. We have isolated two new srPLP/DM20 gene products and identified a new exon of the gene. These products are expressed in neurons as well as oligodendrocytes, and they are localized in the somata of oligodendrocytes and neurons and are absent from the myelin sheath. On the basis of these and other preliminary data, we propose the existence of other products of the PLP/DM20 gene in addition to the """"""""classic"""""""" and sr-PLP/DM20 variants. The overall objective of this application is to isolate and identify these other variants of the PLP/DM20 gene and to examine possible non-myelin functions of the """"""""classic"""""""" PLP and DM20 as well as the variant products of the gene. These include: (1) identifying and characterizing novel products of the PLP/DM20 gene and examining their cellular and regional localization in the developing nervous system; (2)[re-] evaluating the hypothesis that cell death in the jimpy mutant is due solely to toxic effects of the mutated protein by prepare cell lines stably transfected with normal and variant/mutant PLP/DM20 cDNAs and comparing levels of expression in conditionally-immortalized OL lines on cell survival; and (3) examining aspects of the non-myelin roles of PLP/DM20 gene products.
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