Abstract
Paralytic tremor (pt), a hereditary neurological disorder of rabbits is a recessive, X-linked point mutation of the gene for proteolipid protein (PLP) biosynthesis. This mutation results in substitution of histidine36 by glutamine in the PLP molecule and produces severe hypomyelination. In the present study, we investigated the developmental expression of myelin - oligodendrocyte - specific glycolipid markers by means of ELISA assay. While immunoreactivity with antibodies recognising proligodendroblast (POA) antigen was unchanged, only minute amounts of the other glycolipid markers characteristic for more advanced stages of OLs maturation, such as 04 and 01 antigens, were expressed inpt brain. The degree of down-regulation was similar to that for MBP. Concomitantly, the level ofin situ expression of the mutated PLP gene mRNA in glial cells of 14 day oldpt brain was found to be as high as in age-matched controls. Northern blot analysis of developmental PLP gene expression showed a significant deficit of this message inpt brain, but only at more advanced developmental stages. However, aside from changes in myelin structure, no changes in glial cell number or morphology were evident by light microscopic examination ofpt mutants. In contrast, electron microscopy revealed substantial abnormalities inpt oligodendrocyte cytoarchitecture, indicating functional impairment of intracellular transport and utilisation of myelin constituents. Thus, only POA expression is positively correlated with the unchanged content of OLs inpt brain, whereas decreases of 04 and 01 antigens, together with MBP immunoreactivity, are indicators of the degree of hypomyelination. Furthermore, oligodendrocyte differentiation appears to proceed normally inpt mutant brain up to the stage of PLP gene expression. Then, due to intracellular accumulation of this abnormal gene product, synthesis of PLP as well as the other myelin-specific constituents is inhibited by a “feed-back” control mechanism.
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Sypecka, J., Gajkowska, B. & Domañska-Janik, K. Oligodendrocyte development in PLP“pt” mutant rabbits: glycolipid antigens and PLP gene expression. Metab Brain Dis 10, 321–333 (1995). https://doi.org/10.1007/BF02109362
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DOI: https://doi.org/10.1007/BF02109362