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

Nature volume 367, pages 455–459 (1994)Cite this article

Abstract

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 α-(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.

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Authors and Affiliations

  1. Institute for Genetics, University of Cologne, Zülpicher Strasse 47, D-50674, Cologne, Germany

    Harold Cremer

  2. Institute for Genetics, University of Cologne, D-50931, Cologne, Germany

    Rita Lange, Annette Christoph, Markus Plomann, Gaby Vopper, Jürgen Roes, Dagmar Barthels, Klaus Rajewsky & Wolfgang Wille

  3. Sanders Brown Center on Aging, University of Kentucky, Lexington, Kentucky, 40536-0230, USA

    Russell Brown, Stanley Baldwin, Philipp Kraemer & Stephen Scheff

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  1. Harold Cremer
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  3. Annette Christoph
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Cremer, H., Lange, R., Christoph, A. et al. Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning. Nature 367, 455–459 (1994). https://doi.org/10.1038/367455a0

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