pt point mutation in plp gene results in hyperexpression of MOG in hypomyelinated rabbit

Abstract

Myelin/oligodendrocyte glycoprotein (MOG) is a minor myelin protein that belongs to the immunoglobulin gene superfamily and evokes demyelination based on immunological response. Localized preferentially at the external surfaces of myelin sheaths, it is one of the primarily target autoantigens in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Elevated MOG content has been found in the myelin fraction of the rabbits affected by the mild form of paralytic tremor (pt) disease, evoked by natural, point mutation in exon 2 of plp gene. A single T --> transversion results in substitution of histidin36 by glutamine in PLP and it's splicing variant DM-20 molecules. The affected animals, although strictly controlled for pt trait, differ significantly in their phenotypes, distinguished by the severity of neurological symptoms. It was shown that the degree of CNS hypomyelination and deficiency of PLP/DM-20 correlates well with the severity of neurological symptoms and is highest in the most strongly affected animals. Variety of phenotypes generated from pt genotype together with previously observed MOG hyperexpression suggested possible contribution of immunological component to the pt disease. Present studies indicate that MOG expression depends both on the phenotype and the age of affected rabbits and most probably mirrors retardation in myelinogenesis process caused by pt mutation.