Conditional knockout of TOG results in CNS hypomyelination

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• The tumor overexpressed gene (TOG) protein localizes to RNA granules involved in myelin basic protein (MBP) mRNA transport.
• Oligodendrocytes produce myelin, essential for CNS function, and rely on efficient mRNA transport for this process.

Purpose of the Study:

• To investigate the in vivo role of TOG protein in myelinating glia.
• To determine the impact of TOG knockout on oligodendrocyte function and myelination.

Main Methods:

• Conditional knockout of the TOG gene in myelinating glia of mice.
• Assessment of motor function, myelin content, and MBP mRNA localization in TOG-deficient mice.

Main Results:

• TOG knockout mice exhibit severe motor deficits and reduced myelination, particularly in the spinal cord.
• MBP mRNA is retained in oligodendrocyte cell bodies, with significantly reduced MBP protein content, despite normal transcript levels.
• Oligodendrocyte numbers remain normal, suggesting a defect in post-transcriptional regulation or transport.

Conclusions:

• TOG protein is essential for the post-transcriptional regulation of MBP gene expression.
• TOG facilitates MBP mRNA transport and/or translation in oligodendrocyte processes and myelin.
• This highlights a critical role for TOG in ensuring proper myelination and neuronal function.