Abnormal myelinogenesis in the central nervous system of the VF mutant rat with recoverable tremor

The vacuole formation (VF) rat is an autosomal recessive myelin mutant characterized by generalized tremor and vacuole formation within the myelin of the central nervous system (CNS). The tremor is prominent between 4 and 8 weeks of age but thereafter gradually improves. The present study, aimed at producing a detailed description of how the principal lesions evolve, revealed that the VF rat has abnormal vacuoles in the periaxonal space in the spinal cord and that these vacuoles decreased concurrently with the loss of tremor. However, a degree of hypomyelination persisted throughout the CNS after the resolution of periaxonal vacuoles. In situ hybridization for proteolipid protein (PLP) demonstrated that the number of small, round PLP-positive oligodendrocytes increased in the spinal cord of VF rats between 10 and 20 weeks of age, suggesting a disruption of oligodendrocytes' maturation. Activated astrocytes and microglia were also found in the VF rats from 4 weeks of age. Our results indicate that the causative genetic defect of the VF rat is likely to be involved in the formation and maintenance of the CNS myelin.

► Abnormal vacuoles decreased with loss of tremor in the VF rat.
► Hypomyelination persists despite resolution of periaxonal vacuoles.
► Oligodendrocytes' maturation is disrupted.
► The causative gene in the VF rat may have novel functions in the CNS myelination.