Delayed and incomplete myelination in a transgenic mouse mutant with abnormal oligodendrocytes

Abstract

In search of animal models suitable for investigating myelin repair, we have analysed myelinogenesis in a transgenic mouse mutant with delayed myelination, but with a normal life-span. The 2-50 mutant which carries a c-myc gene under the regulation of the myelin basic protein promoter has been described previously (Orian et al.: J Neurosci Res 39:604-612, 1994). Here we show that appropriate mRNA transcripts and their corresponding protein products are generated, but that the accumulation of these products is delayed in transgenic mice with respect to nontransgenic littermates. This phenomenon is associated with aberrant myelin and paucity of normal oligodendrocytes. Myelination appears to be carried out by abnormal, oligodendrocyte-like cells. We propose that the primary defect in the 2-50 mutant is an inability to generate the normal number of mature oligodendrocytes. This mutant represents a novel class of mutant in which oligodendrocyte development and myelination can be studied in the absence of interference with a gene for a structural protein of myelin, in an animal with normal survival. It may also represent a new tool to investigate in vivo gliogenesis and regulatory events bringing about the coordinated regulation of myelin protein synthesis.