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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023322-07
Application #
3406637
Study Section
Neurology C Study Section (NEUC)
Project Start
1985-07-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
7
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Other Domestic Higher Education
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Bongarzone, E R; Foster, L M; Byravan, S et al. (1997) Temperature-dependent regulation of PLP/DM20 and CNP gene expression in two conditionally-immortalized jimpy oligodendrocyte cell lines. Neurochem Res 22:363-72
Pribyl, T M; Campagnoni, C; Kampf, K et al. (1996) The major myelin protein genes are expressed in the human thymus. J Neurosci Res 45:812-9
Jacobs, E C; Arnold, A P; Campagnoni, A T (1996) Zebra finch estrogen receptor cDNA: cloning and mRNA expression. J Steroid Biochem Mol Biol 59:135-45
Pribyl, T M; Campagnoni, C W; Kampf, K et al. (1996) Expression of the myelin proteolipid protein gene in the human fetal thymus. J Neuroimmunol 67:125-30
Pribyl, T M; Campagnoni, C W; Kampf, K et al. (1996) Expression of the myelin basic protein gene locus in neurons and oligodendrocytes in the human fetal central nervous system. J Comp Neurol 374:342-53
Landry, C F; Ellison, J A; Pribyl, T M et al. (1996) Myelin basic protein gene expression in neurons: developmental and regional changes in protein targeting within neuronal nuclei, cell bodies, and processes. J Neurosci 16:2452-62
Foster, L M; Landry, C; Phan, T et al. (1995) Conditionally immortalized oligodendrocyte cell lines migrate to different brain regions and elaborate 'myelin-like' membranes after transplantation into neonatal shiverer mouse brains. Dev Neurosci 17:160-70
Ueno, S; Foster, L; Hifumi, G T et al. (1995) The simian virus 40 large T antigen does not inhibit translation of the 14-kDa myelin basic protein mRNA in reticulocyte lysates or in transfected cells. J Neurochem 64:928-31
Kashima, T; Vinters, H V; Campagnoni, A T (1995) Unexpected expression of intermediate filament protein genes in human oligodendroglioma cell lines. J Neuropathol Exp Neurol 54:23-31
Byravan, S; Campagnoni, A T (1994) Serum factors and hydrocortisone influence the synthesis of myelin basic proteins in mouse brain primary cultures. Int J Dev Neurosci 12:343-51

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