Abstract

The objective of this umbrella project is the detailed understanding of the developmental program that culminates in myelin synthesis. We are particularly interested in obtaining molecular level information about the control of expression of the myelin basic protein gene and the proteolipid protein gene. To this end, we cDNA cloned and sequenced both human and mouse myelin basic protein mRNA and proteolipid protein mRNA. We used these characterized cDNAs to identify and study the organization of the genes encoding them. Our results demonstrate conclusively that the multiple forms of myelin basic protein which are found in both man and mouse originate from a mechanism of alternative splicing of the nascent gene transcript. Genes of two mutant mice have also been well characterized. The Shiverer mouse was found to have a massive deletion in the myelin basic protein gene, whereas the Jimpy mouse has a small deletion in the proteolipid protein gene. Consequently, neither mutant mouse is able to synthesize myelin and both mutants suffer from a neurological disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002528-05
Application #
3968990
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
National Institute of Neurological Disorders and Stroke
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Hudson, Lynn D; Romm, Elena; Berndt, Jo Ann et al. (2011) A tool for examining the role of the zinc finger myelin transcription factor 1 (Myt1) in neural development: Myt1 knock-in mice. Transgenic Res 20:951-61
Szuchet, Sara; Nielsen, Joseph A; Lovas, Gabor et al. (2011) The genetic signature of perineuronal oligodendrocytes reveals their unique phenotype. Eur J Neurosci 34:1906-22
Nielsen, Joseph A; Lau, Pierre; Maric, Dragan et al. (2009) Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis. BMC Neurosci 10:98
Lau, Pierre; Verrier, Jonathan D; Nielsen, Joseph A et al. (2008) Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes. J Neurosci 28:11720-30
Nielsen, Joseph A; Maric, Dragan; Lau, Pierre et al. (2006) Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling. J Neurosci 26:9881-91
Kim, Hyunsook; Barton, Elisabeth; Muja, Naser et al. (2005) Intact insulin and insulin-like growth factor-I receptor signaling is required for growth hormone effects on skeletal muscle growth and function in vivo. Endocrinology 146:1772-9
Romm, Elena; Nielsen, Joseph A; Kim, Jin G et al. (2005) Myt1 family recruits histone deacetylase to regulate neural transcription. J Neurochem 93:1444-53
Nielsen, Joseph A; Berndt, Jo Ann; Hudson, Lynn D et al. (2004) Myelin transcription factor 1 (Myt1) modulates the proliferation and differentiation of oligodendrocyte lineage cells. Mol Cell Neurosci 25:111-23
Muja, Naser; Lovas, Gabor; Romm, Elena et al. (2004) Expression of a catalytically inactive transmembrane protein tyrosine phosphatase epsilon (tm-PTP epsilon) delays optic nerve myelination. Glia 48:278-97
Hudson, Lynn D (2003) Pelizaeus-Merzbacher disease and spastic paraplegia type 2: two faces of myelin loss from mutations in the same gene. J Child Neurol 18:616-24

Showing the most recent 10 out of 22 publications