Abstract

Mouse central nervous system contains a family of polypeptides that are structurally related to myelin basic protein (MBP). A variety of genetic determinants and epigenetic factors have been identified that regulate the expression of MBP-related gene products in the mouse brain. In this application we propose to analyze the structures of the different MBP-related gene products by cloning and sequencing MBP-specific cDNA from mouse brain. We will use restriction fragment length polymorphisms associated with MBP-specific sequences in inbred and recombinant inbred mouse genomic DNA to determine the chromosomal locations of MBP structural gene(s) and MBP regulator genes. We will use MBP-specific cDNA probes to study MBP gene expression in wild type and mutant mouse brain and in primary cultures of mouse and rat brain. The results will: delineate and characterize the genetic and epigenetic factors that regulate MBP gene expression in the brain, reveal the molecular mechanisms responsible for the structural polymorphism of MBP-related gene products and for regulating their expression, and elucidate the functional relationship between MBP gene expression and myelin morphogenesis. This will further our understanding of the pathogenesis of a variety of birth defects and degenerative diseases that affect myelin in humans.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS015190-09
Application #
3396044
Study Section
Neurology C Study Section (NEUC)
Project Start
1979-04-01
Project End
1988-11-30
Budget Start
1987-04-01
Budget End
1988-11-30
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Connecticut
Department
Type
School of Medicine & Dentistry
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030

  Publications

Falkenberg, Cibele Vieira; Carson, John H; Blinov, Michael L (2017) Multivalent Molecules as Modulators of RNA Granule Size and Composition. Biophys J 113:235-245
Giampetruzzi, Anthony; Carson, John H; Barbarese, Elisa (2013) FMRP and myelin protein expression in oligodendrocytes. Mol Cell Neurosci 56:333-41
Tatavarty, Vedakumar; Ifrim, Marius F; Levin, Mikhail et al. (2012) Single-molecule imaging of translational output from individual RNA granules in neurons. Mol Biol Cell 23:918-29
Chen, Yan; Bai, Ping; Mackay, Shannon et al. (2011) Herpes simplex virus type 1 helicase-primase: DNA binding and consequent protein oligomerization and primase activation. J Virol 85:968-78
Francone, Victor P; Ifrim, Marius F; Rajagopal, Chitra et al. (2010) Signaling from the secretory granule to the nucleus: Uhmk1 and PAM. Mol Endocrinol 24:1543-58
Han, Siew Ping; Friend, Lexie R; Carson, John H et al. (2010) Differential subcellular distributions and trafficking functions of hnRNP A2/B1 spliceoforms. Traffic 11:886-98
Levin, Mikhail K; Hingorani, Manju M; Holmes, Raquell M et al. (2009) Model-based global analysis of heterogeneous experimental data using gfit. Methods Mol Biol 500:335-59
Eisenberg, Shlomo; Korza, George; Carson, John et al. (2009) Novel DNA binding properties of the Mcm10 protein from Saccharomyces cerevisiae. J Biol Chem 284:25412-20
Paradise, Allison; Levin, Mikhail K; Korza, George et al. (2007) Significant proportions of nuclear transport proteins with reduced intracellular mobilities resolved by fluorescence correlation spectroscopy. J Mol Biol 365:50-65
Kosturko, Linda D; Maggipinto, Michael J; Korza, George et al. (2006) Heterogeneous nuclear ribonucleoprotein (hnRNP) E1 binds to hnRNP A2 and inhibits translation of A2 response element mRNAs. Mol Biol Cell 17:3521-33

Showing the most recent 10 out of 28 publications