DELAYED AND INCOMPLETE MYELINATION IN A TRANSGENIC MOUSE MUTANT WITH ABNORMAL OLIGODENDROCYTES

In search of animal models suitable for investigating myelin repair, w e have analysed myelinogenesis in a transgenic mouse mutant with delay ed myelination, but with a normal life-span, The 2-50 mutant which car ries a c-myc gene under the regulation of the myelin basic protein pro moter has been described previously (Orian et al.: J Neurosci Res 39:6 04-612, 1994), Here we show that appropriate mRNA transcripts and thei r corresponding protein products are generated, but that the accumulat ion of these products is delayed in transgenic mice with respect to no ntransgenic littermates. This phenomenon is associated with aberrant m yelin and paucity of normal oligodendrocytes, Myelination appears to b e 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 no vel class of mutant in which oligodendrocyte development and myelinati on can be studied in the absence of interference with a gene for a str uctural protein of myelin, in an animal with normal survival, It may a lso represent a new tool to investigate in vivo gliogenesis and regula tory events bringing about the coordinated regulation of myelin protei n synthesis. (C) 1997 Wiley-Liss, Inc.