The regulation of expression of the genes coding for myelin proteins is an important problem about which relatively little is known. The overall goal of this project is to examine the structural organization of these genes, beginning with those coding for the myelin basic proteins. In mice, four structurally-related myelin basic proteins exist and, although it is clear that four separate mRNAs code for these proteins, it is not yet known whether or not these proteins are specified by separate genes. With the availability of a cDNA probe to a part of the mouse myelin basic protein common to all four species, it is now possible to isolate MBP genes from a mouse genomic library and study their structure and organization. Two MBP clones have already been obtained which appear to be different from each other, suggesting that the mouse MBPs are coded for by more than one gene. These clones and the original cDNA clone will be used to determine the number of MBP genes in the mouse genome. Each gene will then be isolated from a genomic library and characterized by restriction enzyme analysis and sequencing of selected regions. The sequence information will be used to classify the MBP genes according to the type of MBP protein each codes for. The sequences will also be examined to identify potential regulatory sequences and splice sites and correlated with R-looping results and sequence data from cloned hybrid selected MBP mRNAs to identify introns. In the process of isolating and sequencing these genes, fragments of the genes will be subcloned and these fragments may prove to contain unique sequences which might be used as probes to discriminate the various MBP genes. The MBP cDNA probe will also permit the examination of the structure of the MBP genes in the dysmyelinating mutant mice, jimpy and shiverer. These two dysmyelinating mutants are defective in their ability to synthesize normal levels of the myelin basic proteins. Southern blots will be used to determine whether gross alterations exist in the structures of the MBP genes in these mutants. In addition, genomic libraries of the mutants will be prepared and the MBP genes will be isolated from these libraries and studied for sequence differences which may account for the mutant phenotype. In this way, structural alterations in the MBP genes or their controlling elements will be identified.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023322-02
Application #
3406634
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-07-01
Project End
1987-12-31
Budget Start
1986-07-01
Budget End
1987-12-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Hospitals
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 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
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
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

Showing the most recent 10 out of 43 publications