Abnormal myelinogenesis both in the white and gray matter of the attractin-deficient mv rat

Abstract

The myelin vacuolation (mv) rat exhibits hypomyelination and vacuole formation in the myelin throughout the CNS, caused by a null mutation in the attractin gene. Myelin alterations in the spinal cord of mv rats progress during postnatal development and are more prominent in the white matter. In contrast, microglial activation is confined to the gray matter of mv rats. We here investigate the distribution and expression patterns of major CNS myelin proteins in the spinal cord of mv rats during the development of the myelin lesions. Immunohistochemical and Western blot analyses demonstrated a considerable reduction in the expression of major CNS myelin proteins both in the white and gray matter of mv rats, which was consistent with the morphological alterations of myelin sheaths. Real-time PCR analysis revealed a significant decrease in expression of proteolipid protein (PLP) mRNA both in the white and gray matter of mv rats. However, there was no significant difference between control and mv rats in the cell number of PLP mRNA-positive oligodendrocytes either in the white or gray matter, suggesting an impairment of myelin protein production by oligodendrocytes. Our results indicate that myelinogenesis but not oligodendrogenesis is severely altered both in the white and gray matter of mv rats.