Reduced levels of a specific myelin-associated oligodendrocytic basic protein isoform in shiverer myelin
P Montague1, D Kirkham, A S McCallion
1Applied Neurobiology Group, Department of Veterinary Clinical Studies, University of Glasgow, Bearsden, UK.P.Montague@vet.gla.ac.uk
Abstract:
Myelin-associated oligodendrocytic basic protein (MOBP) and myelin basic protein (MBP) share many structural similarities. MOBP is synthesised by mature oligodendrocytes and localised at the major dense line (MDL), suggesting a role in the myelin compaction process. The shiverer mouse, a deletion mutant of the myelin basic protein (Mbp) gene, has poorly compacted myelin with essentially no MDL. In this study we compare the developmental expression of the Mobp gene in wild-type and shiverer mice. The significant finding is that one of the two abundant MOBP isoforms, the approximately 20-kD species, is poorly incorporated into shiverer myelin. The absence is specific to shiverer and is not a feature of dysmyelinating mutants with an abnormal intraperiod line. Our data suggest that incorporation of this MOBP isoform into shiverer myelin may be influenced by the presence of MBP or be a consequence of a disrupted MDL.
Insights
Myelin-associated oligodendrocytic basic protein (MOBP) incorporation into myelin is impaired in shiverer mice lacking myelin basic protein (MBP). This suggests MBP influences MOBP integration, crucial for myelin compaction.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Myelin basic protein (MBP) and myelin-associated oligodendrocytic basic protein (MOBP) are key myelin proteins with structural similarities.
- MOBP is synthesized by oligodendrocytes and localized to the major dense line (MDL), indicating a role in myelin compaction.
- The shiverer mouse model exhibits poorly compacted myelin due to Mbp gene deletion and lacks a proper MDL.
Purpose of the Study:
- To investigate the developmental expression of the Mobp gene in wild-type versus shiverer mice.
- To determine the impact of Mbp gene deletion on MOBP incorporation into myelin.
Main Methods:
- Comparative analysis of Mobp gene expression during development.
- Assessment of MOBP isoform incorporation into myelin in wild-type and shiverer mouse models.
Main Results:
- One of the two abundant MOBP isoforms (approximately 20-kD) is poorly incorporated into the myelin of shiverer mice.
- This incorporation defect is specific to the shiverer mutation and not observed in other dysmyelinating mutants affecting the intraperiod line.
- The absence of MBP in shiverer mice significantly affects MOBP isoform integration.
Conclusions:
- The incorporation of a specific MOBP isoform into myelin is dependent on the presence of MBP.
- Disruption of the major dense line (MDL) in shiverer mice may contribute to the impaired incorporation of MOBP.
- These findings highlight the intricate relationship between myelin proteins and structural integrity during myelination.
