Nature 367, 455 - 459 (03 February 1994); doi:10.1038/367455a0

Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning

Harold Cremer^*, Rita Lange^†, Annette Christoph^†, Markus Plomann^†, Gaby Vopper^†, Jürgen Roes^†, Russell Brown^‡, Stanley Baldwin^‡, Philipp Kraemer^‡, Stephen Scheff^‡, Dagmar Barthels^†, Klaus Rajewsky^† & Wolfgang Wille^†

^* Institute for Genetics, University of Cologne, Zülpicher Strasse 47, D-50674 Cologne, Germany
^† Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
^‡ Sanders Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536-0230, USA

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 -(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.

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