ABSENCE OF THE MYELIN-ASSOCIATED GLYCOPROTEIN (MAG) AND THE NEURAL CELL-ADHESION MOLECULE (N-CAM) INTERFERES WITH THE MAINTENANCE, BUT NOT WITH THE FORMATION OF PERIPHERAL MYELIN

We have previously shown that mice deficient in the gene for the myeli n-associated glycoprotein (MAG) develop normal myelin in the periphera l nerves, but show axon and myelin degeneration at eight months of age , suggesting that MAG is involved in the maintenance of axon-Schwann c ell integrity. The search for molecules that might replace MAG during myelination revealed an overexpression of the neural cell adhesion mol ecule (N-CAM) at those aspects where MAG is detectable in wild type mi ce. To test whether N-CAM might compensate for MAG during myelination in MAG-deficient mice, double mutants deficient in both MAG and N-CAM (MAG(-)/N-CAM(-) mice) were generated by cross-breeding the single mut ants. Whereas alterations of myelin development were not detectable in either of the single or double mutants, degeneration of myelin and ax ons occurred approximately 4 weeks earlier in MAG(-)/N-CAM(-) than in MAG(-) mutants. Furthermore, at 8 weeks of age, single fiber preparati on and electron microscopy revealed that the number of profiles indica tive of degeneration was substantially increased in MAG(-)/N-CAM(-) mu tants when compared to MAG(-) mice. These data suggest that in MAG-def icient mice N-CAM does not compensate for MAG in myelin formation but partially substitutes for it in the maintenance of axon-myelin integri ty.