Cellular responses in the spinal cord during development of hypomyelination in the mv rat

The myelin vacuolation (mv) rat is an autosomal recessive mutant characterized by hypomyelination and vacuole formation in the myelin throughout the central nervous system (CNS). Previous genetic studies have revealed a null mutation in attractin gene of the mv mutant rat. It has been known that mutation at the attractin locus results in myelin alterations, but their detailed pathogenesis is still unclear. In this study, we examined glial changes in the spinal cord of mv rats at 2, 4, 6, and 8 weeks of age and identified attractin-expressing cells in the rat spinal cord. No abnormality was found in the number and morphology of oligodendrocytes in mv rats at any of the ages examined, although the severity and extent of myelin disorder increased with age. Coincident with the myelin abnormalities, there was progressive astrogliosis from 2 weeks. Marked microglial activation was observed exclusively in the gray matter of mv rats from 6 weeks, coincident with severe myelin disruption. A double-labeling study demonstrated that attractin-expressing cells are mostly oligodendrocytes in the white matter of the spinal cord of wild-type rats, whereas no attractin-positive cells were detected in mv rats. Previous study demonstrated that Luxol fast blue staining pattern and immunoreactivity for myelin basic protein were decreased in mv rats. Therefore, this study indicates that the attractin defect results in oligodendrocyte dysfunction, and is associated with astrogliosis and microglial activation in mv rats. The data suggest that attractin may be directly involved in the function of oligodendrocytes in CNS myelination.