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 splicing ^1-3. 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 neurulation^4, axonal outgrowth⁵, histogenesis of the retina^6,7 and development of the olfactory system^8-10 are correlated with the regulated expression of N-CAMs^11-14. 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 α-(2,8)-linked polysialic acid, a carbohydrate structure thought to be correlated with neural development and plasticity^15,16. The animals showed deficits in spatial learning when tested in the Morris water maze¹⁷, whereas activity and motor abilities appeared normal.