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Published on: February 17, 2016
Dysmyelination and reduced myelin basic protein gene expression by oligodendrocytes of SHP-1-deficient mice
Paul T Massa1, Charlene Wu, Karen Fecenko-Tacka
1Department of Neurology, Neuroscience Program, SUNY Upstate Medical University, Syracuse, New York 13066, USA. massap@upstate.edu
Abstract:
We have shown previously that myelin-forming oligodendrocytes express the protein tyrosine phosphatase SHP-1 and that myelin formation was decreased in SHP-1-deficient motheaten mice compared to that in normal littermates. These studies suggested a potential importance for SHP-1 in oligodendrocyte and myelin development. To address further this possibility, we analyzed myelin formation by microscopy and myelin basic protein (MBP) gene expression in motheaten mice at ages when myelination occurs in the developing central nervous system (CNS). Furthermore, we correlate these findings with MBP gene expression in oligodendrocytes grown in vitro. We have found that CNS myelination was significantly reduced in SHP-1-deficient mice relative to their normal littermates at multiple times during the active period of myelination. Under electron microscopy, greater numbers of axons in spinal cords of motheaten mice were either unmyelinated or had thinner myelin sheathes compared to those in matched areas of normal littermates. Accordingly, MBP protein and mRNA levels were reduced in SHP-1-deficient mice compared to that in the CNS of normal littermates. In vitro, O1(+) oligodendrocytes from motheaten mice expressed much less MBP than O1(+) oligodendrocytes of normal littermates indicating an alteration in oligodendrocyte differentiation. The latter correlated with reduced MBP mRNA relative to cerebroside galactosyl transferase (CGT) gene mRNA in SHP-1-deficient oligodendrocytes in purified cultures. We propose that SHP-1 is a critical regulator of developmental signals leading to terminal differentiation and myelin sheath formation by oligodendrocytes.
Insights
Protein tyrosine phosphatase SHP-1 is crucial for central nervous system (CNS) myelination. SHP-1 deficiency in mice significantly reduces myelin sheath formation and oligodendrocyte differentiation, impacting myelin basic protein (MBP) expression.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Oligodendrocytes are glial cells responsible for myelin sheath formation in the CNS.
- Previous studies indicated protein tyrosine phosphatase SHP-1 expression in oligodendrocytes and its potential role in myelin development.
- SHP-1-deficient motheaten mice exhibit decreased myelin formation compared to normal littermates.
Purpose of the Study:
- To further investigate the role of SHP-1 in oligodendrocyte development and CNS myelination.
- To analyze myelin formation and myelin basic protein (MBP) gene expression in SHP-1-deficient mice during active myelination periods.
- To correlate in vivo findings with in vitro studies of oligodendrocyte differentiation.
Main Methods:
- Microscopic analysis of CNS myelination in SHP-1-deficient and normal littermate mice.
- Electron microscopy to assess axon myelination and myelin sheath thickness.
- Measurement of myelin basic protein (MBP) and cerebroside galactosyl transferase (CGT) mRNA and protein levels.
- In vitro culture of oligodendrocytes from motheaten and normal mice to assess differentiation and MBP expression.
Main Results:
- CNS myelination was significantly reduced in SHP-1-deficient mice compared to normal littermates.
- Electron microscopy revealed more unmyelinated axons and thinner myelin sheaths in SHP-1-deficient mice.
- MBP protein and mRNA levels were decreased in the CNS of SHP-1-deficient mice.
- In vitro, oligodendrocytes from motheaten mice showed reduced MBP expression and differentiation, correlating with lower MBP mRNA relative to CGT mRNA.
Conclusions:
- SHP-1 plays a critical role in regulating developmental signals essential for oligodendrocyte terminal differentiation.
- SHP-1 is vital for proper myelin sheath formation in the developing central nervous system.
- These findings highlight SHP-1 as a key regulator of myelination processes.
