Phosphatase PP2A is Required for CNS Myelination via Proteasome‐Dependent Regulation of Sox10 Expression

Loss‐of‐function mutations on phosphatase PP2A subunits are known to cause diseases with hypomyelination and defective motor functions, but the underlying mechanisms remain unknown. Here we generate a mutant mouse in which the catalytic subunit PP2Acα is inactivated in oligodendrocyte (OL) lineage cells in the central nervous system. We show that PP2A mutant mice exhibit deficient oligodendrogenesis and are impaired specifically in a fine motor coordination and balance task. We demonstrate that inactivation of PP2Acα leads to down‐regulation of SOX10 in a proteasome‐dependent manner. Overall, this study provides insights on mechanisms for white matter abnormalities caused by loss of PP2A function. The findings in this study may be implicated in the pathogenesis of diseases with defective motor coordination.