Disturbed oligodendrocyte development and recovery from hypomyelination in a c-myc transgenic mouse mutant.

Abstract

The complexity of interactions underlying the elaboration of myelin has been extensively demonstrated. We provide evidence that signals promoting myelination are not confined to the normal developmental time window for myelination and persist well into adult life. The 2-50 mutant, described previously, carries a c-myc transgene regulated by a myelin basic protein promoter. This mutant is characterised by severe hypomyelination and abnormal oligodendrocytes in early life, followed by loss of the phenotype and normal longevity. We show that c-myc expression in early oligodendrocyte development results in a substantial reduction of cells of this lineage. However, apparent complete recovery, associated with loss of c-myc expression, axonal survival, and gradual myelin accumulation, is observed by 4 months of age. Thus, stimulation of myelination continues during adult life until normal myelin levels are established. We propose that this mutant may contribute to the characterisation of oligodendrocyte responses to myelinating signals.