OVEREXPRESSION OF 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE IN TRANSGENIC MICE ALTERS OLIGODENDROCYTE DEVELOPMENT AND PRODUCES ABERRANT MYELINATION

The function of the intracellular protein 2',3'-cyclic nucleotide 3'-p hosphodiesterase (CNP) of oligodendrocytes (ODC) is unknown, We have n ow generated several homozygous transgenic mouse lines in which the hu man CNP gene is overexpressed up to sixfold, revealing new insights in to early stages of myelinogenesis. Although no behavioral phenotype is immediately apparent, abnormalities of ODC and their myelin sheaths a re striking. These are manifested as redundant myelin membrane and int ramyelenic vacuoles, as well as lack of myelin compaction concordant w ith failure of the cytoplasmic leaflets of compact myelin to fuse. Fur ther, ODC that overexpress CNP appear to mature earlier in development , resulting in earlier maximum gene expression for myelin basic protei ns and proteolipid protein, These results indicate that CNP is an earl y expressed regulator of cellular events that culminate in CNS myelina tion.