STRUCTURAL ORGANIZATION OF MYELIN PROTEIN GENES

在本申请中，正在测试的假设是， 碱性蛋白（MBP）基因比原来想象的要复杂， 并且该基因的一部分在mRNA中表达， MBPs。 我们有证据表明， 少突胶质细胞，其由重叠或 是MBP基因的一部分。 该MBP基因-Cl相关产品是 表达于少突胶质细胞（或其前体）和 脾脏 在少突胶质细胞中，这些mRNA的表达与 与大多数人不同的发展模式 MBP mRNA。 本项目的总体目标是检查 该基因的结构和组织，以确定其表达 在少突胶质细胞中，并推断它在 少突胶质细胞分化通过检查其 在少突胶质细胞和免疫系统细胞中表达。 我们建议完成分离、表征和分析 在这些mRNA中，我们目前只分离出40%的 整个消息。 基因的结构将由 外显子/内含子结构及其结构关系 与MBP基因有关 初步证据表明， 在未成熟的少突胶质细胞或其前体中表达 细胞 因此，细胞类型和发育阶段在 将确定哪些少突胶质细胞表达该基因。 还将进行实验来破坏基因的表达 与反义寡脱氧核苷酸，并检查随后的 少突胶质细胞的分化。 表达的个体发生 将在体内和体外的几个基因进行检查， 免疫相关组织和细胞系， 杂交法测定B细胞和T细胞的分期 表达发生的发展。 假设是 在这些实验和那些处理少突胶质细胞的实验中， 差异的另一个重要原因是，该基因在 少突胶质细胞的分化。 我们认为这可能是 可能阐明该基因在少突胶质细胞中的作用， 通过检查其在免疫系统中的表达， B细胞和T细胞分化是很好理解的。

In this application the hypothesis is being tested that the myelin basic protein (MBP) gene is more complex than originally thought, and that parts of the gene are expressed in mRNAs that do not encode MBPs. We have evidence for the expression of an mRNA in oligodendrocytes which is encoded by a gene that either overlaps or forms a part of the MBP gene. This MBP gene-Cl related product is expressed in oligodendrocytes (or their precursors) and in the spleen. In the oligodendrocyte, these mRNAs are expressed according to a different developmental pattern than that of the majority of MBP mRNAs. The overall goal of this project is to examine the structure and organization of this gene, to determine its expression in oligodendrocytes, and to deduce the role it plays during oligodendrocyte differentiation through an examination of its expression in both oligodendrocytes and cells of the immune system. We propose to complete the isolation, characterization and analysis of these mRNAs for which we currently have isolated only 40% of the entire message. The structure of the gene will be determined with respect to its exon/intron structure and its structural relationship to the MBP gene. Preliminary evidence indicates that the gene is expressed in either immature oligodendrocytes or their precursor cells. Accordingly, the cell type and the developmental stage at which oligodendrocytes express the gene will be determined. Experiments also will be performed to disrupt expression of the gene with antisense oligodeoxynucleotides and examine the subsequent differentiation of the oligodendrocyte. The ontogeny of expression of the gene will be examined in vivo and in vitro in several immunologically relevant tissues and cell lines by in situ hybridization to determine the stage of B cell and T cell development at which expression occurs. The hypothesis being examined in these experiments and those dealing with oligodendrocyte differentiation is that the gene plays some role in the differentiation of the oligodendrocyte. We believe that it may be possible to elucidate the role of this gene in oligodendrocytes through an examination of its expression in the immune system, where B cell and T cell differentiation is well understood.