Functional analysis of attractin (Atrn) using a mutant rat with attractin deficiency

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mv (myelin vacuolation) is a mutant rat characterized by vacuolation in the central nervous system and lesion is caused by a null mutation in attractin gene. This project was aimed to clarify the pathogenesis of mv rat and to analyze the function of attractin protein for myelination and maintenance in myelin. We used 2-24 week-old mv and control (heterozygote or wild type). Frozen sections were prepared from the lumber spinal cord and immunohistochemistry was conducted using antibody against CNP, GFAP, OX-42, and OX-6 to evaluate the kinetics of various glial cells. To study the kinetics of oligodendrocyte and precursor of oligodendrocyte, in situ hybridization was also carried out using RNA probes against PLP and PDGF alpha-receptor mRNA. Hypomyelination, attenuation and splitting of myelin were found in the spinal cords from 2 weeks of mv rat. Myelin lesion gradually deteriorated with ageing. There is no statistic differences in the number of oligodendrocytes between the mv and control rats. Increasing and hypertrophic astrocytes were observed from 2 weeks of mv rat and these activated astrocytes distributed in the myelin lesion, suggesting a close correlation between the myelin lesion and activation of astrocytes. Many activated microglias were found in the gray matter of spinal cord rather than the white matter where marked myelin lesion were noted. No obvious differences in number of PLP positive and PDFF alpha-receptor positive cells. These findings suggested that absence of attractin causes an activation of microglia and dysfunction in myelin indirectly.