Myelin-associated glycoprotein (MAG) is a 100,000 dalton component of the myelin membrane. The molecule is similar in structure to neural cell adhesion molecules and it has been proposed that MAG may mediate cell-cell interactions during the initial stages of myelinogenesis. In previous studies, supported by this grant, we have characterized MAG in rat brain by molecular cloning, determined the structure of the rat MAG gene and analyzed the expression of MAG mRNAs and protein in the rodent nervous system. The studies proposed here will focus on the structure of the MAG gene, the mechanisms of its regulation during myelination and remylination, and attempts to understand the function of MAG by disrupting its expression. It is the aim of the proposed studies to: 1. Analyze the mechanisms of regulation of the MAG gene. 2. Generate transgenic mice expressing regulatory regions of the MAG gene and to analyse the expression of the MAG gene in vivo. 3. Analyse the expression of the MAG gene during remyelination following a demyelinating viral infection of the central nervous system. 4. Disrupt the expression of the MAG gene, in order to asses the functional consequences of decreased or absent MAG expression on myelinogenesis. 5. Investigate the genetic defects in the mouse mutant quivering and the relationship of this mutation to the MAG gene. MAG appears to play a critical role in the early stages of myelinogenesis by mediating the initial contact between the myelinating cell and the axon and it is likely that MAG plays a similar role in remyelination following a demyelinating disease. A detailed understanding of the factors that regulate the expression of MAG will be essential for designing therapies to encourage the formation of new myelin in diseases such as multiple sclerosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS020728-07
Application #
3401282
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1984-04-01
Project End
1991-12-31
Budget Start
1991-07-20
Budget End
1991-12-31
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Milner, R J (1990) Differential cloning approaches to the nervous system. Ann N Y Acad Sci 579:273-80
Milner, R J; Bloom, F E; Sutcliffe, J G (1987) Brain-specific genes: strategies and issues. Curr Top Dev Biol 21:117-50
Lai, C; Brow, M A; Nave, K A et al. (1987) Two forms of 1B236/myelin-associated glycoprotein, a cell adhesion molecule for postnatal neural development, are produced by alternative splicing. Proc Natl Acad Sci U S A 84:4337-41
Lai, C; Watson, J B; Bloom, F E et al. (1987) Neural protein 1B236/myelin-associated glycoprotein (MAG) defines a subgroup of the immunoglobulin superfamily. Immunol Rev 100:129-51
Milner, R J; Randolph, L; Bahr, D et al. (1987) Molecular biological approaches to the brain and their application to the study of alcoholism. Prog Clin Biol Res 241:291-302
Miller, F D; Naus, C C; Higgins, G A et al. (1987) Developmentally regulated rat brain mRNAs: molecular and anatomical characterization. J Neurosci 7:2433-44
Lenoir, D; Battenberg, E; Kiel, M et al. (1986) The brain-specific gene 1B236 is expressed postnatally in the developing rat brain. J Neurosci 6:522-30
Milner, R J; Lai, C; Lenoir, D et al. (1986) Brain-specific gene expression. Biochem Soc Symp 52:107-17
Bloom, F E; Battenberg, E; Ferron, A et al. (1985) Neuropeptides: interactions and diversities. Recent Prog Horm Res 41:339-67
Bloom, F E; Battenberg, E L; Milner, R J et al. (1985) Immunocytochemical mapping of 1B236, a brain-specific neuronal polypeptide deduced from the sequence of a cloned mRNA. J Neurosci 5:1781-802

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