INACTIVATION OF THE N-CAM GENE IN MICE RESULTS IN SIZE-REDUCTION OF THE OLFACTORY-BULB AND DEFICITS IN SPATIAL-LEARNING

NEURAL-CELL adhesion molecules (N-CAMs) are members of the immunoglobulin superfamily mediating homo- and heterophilic cell-cell interactions. N-CAM exists in various isoforms which are generated by alternative splicing1-3. During embryonic development, N-CAMs are expressed in derivatives of all three germ layers, whereas in the adult animal they are predominantly present in neural tissue. Processes like neurulation4, axonal outgrowth5, histogenesis of the retina6,7 and development of the olfactory system8-10 are correlated with the regulated expression of N-CAMs11-14. We show here that N-CAM-deficient mice generated by gene targeting appear healthy and fertile, but adult mutants show a 10% reduction in overall brain weight and a 36% decline in size of the olfactory bulb. N-CAM deficiency coincides with almost total loss of protein-bound alpha-(2,8)-linked polysialic acid, a carbohydrate structure thought to be correlated with neural development and plasticity15,16. The animals showed deficits in spatial learning when tested in the Morris water maze17, whereas activity and motor abilities appeared normal.