STRUCTURAL ORGANIZATION OF MYELIN PROTEIN GENES

在这个应用中，我们正在检验一种假设，即髓鞘 碱性蛋白(MBP)基因比最初认为的更复杂， 基因的某些部分在不编码的mRNA中表达 Mbps。我们有证据证明一种基因在 少突胶质细胞，由重叠或重叠的基因编码 形成了MBP基因的一部分。该MBP基因-CL相关产物是 在少突胶质细胞(或其前体)和在 脾。在少突胶质细胞中，这些mRNAs的表达 发展到与大多数人不同的发展模式 MBP mRNAs。这个项目的总体目标是研究 该基因的结构和组织，以确定其表达 在少突胶质细胞中表达，并推断其在 少突胶质细胞分化的ITS检测 在少突胶质细胞和免疫系统细胞中均有表达。 我们建议完成分离、表征和分析 在这些我们目前只分离出40%的 完整的消息。基因的结构将通过以下方式确定 关于其外显子/内含子结构及其结构关系 MBP基因。初步证据表明，该基因是 在未成熟少突胶质细胞或其前体细胞中表达 细胞。相应地，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。 还将进行实验以干扰基因的表达 与反义寡核苷酸结合，检测随后的 少突胶质细胞的分化。表达的个体发生学 将在体内和体外对几个 免疫相关组织和细胞系的原位检测 杂交法确定B细胞和T细胞的分期 表达发生的发展阶段。假设是 在这些实验和那些处理少突胶质细胞的实验中被检查 分化是指该基因在 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 通过检查它在免疫系统中的表达，其中 B细胞和T细胞的分化是众所周知的。

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.