Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning (2024)

Abstract

NEURAL-CELL adhesion molecules (N-CAMs) are members of the immunoglobulin superfamily mediating hom*o- 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.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Change institution

Buy or subscribe

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Learn more

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning (1)

Overexpression of schizophrenia susceptibility factor human complement C4A promotes excessive synaptic loss and behavioral changes in mice

Article 22 December 2020

Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning (2)

Spatiotemporal expression of IgLON family members in the developing mouse nervous system

Article Open access 01 October 2021

Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning (3)

Elevated expression of complement C4 in the mouse prefrontal cortex causes schizophrenia-associated phenotypes

Article 09 April 2021

References

  1. Hemperly, J. J., Murray, B. A., Edelman, G. M. & Cunningham, B. A. Proc. natn. Acad. Sci. U.S.A. 83, 3037–3041 (1986).

    Article CAS ADS Google Scholar

  2. Barthels, D. et al. EMBO J. 6, 907–914 (1987).

    Article CAS Google Scholar

  3. Barthels, D., Vopper, G., Boned, A., Cremer, H. & Wille, W. Eur. J. Neurosci. 4, 327–337 (1992).

    Article Google Scholar

  4. Crossin, K. L., Prieto, A. L., Hoffmann, S., Jones, F. & Friedlander, D. R. Expl Neurol. 109, 6–18 (1990).

    Article CAS Google Scholar

  5. Tosney, K. W., Watanabe, M., Landmesser, L. & Rutishauser, U. Devl Biol. 114, 437–452 (1986).

    Article CAS Google Scholar

  6. Thiery, J.-P., Brackenbury, R., Rutishauser, U. & Edelman, G. M. J. biol. Chem. 252, 6841–6845 (1977).

    CAS PubMed Google Scholar

  7. Silver, J. & Rutishauser, U. Devl Biol. 106, 485–499 (1984).

    Article CAS Google Scholar

  8. Key, B. & Akeson, R. A. J. Cell Biol. 110, 1729–1743 (1990).

    Article CAS Google Scholar

  9. Key, B. & Akeson, R. A. Neuron 6, 381–396 (1991).

    Article CAS Google Scholar

  10. Chung, W. W., Lagenaur, C. F., Yimin, Y. & Lund, J. S. J. comp. Neurol. 314, 290–305 (1991).

    Article CAS Google Scholar

  11. Edelman, G. M. Biochemistry 27, 3534–3543 (1988).

    Article Google Scholar

  12. Jessell, T. M. Neuron 1, 3–13 (1990).

    Article Google Scholar

  13. Rutishauser, U. & Jessel, T. M. Physiol. Rev. 68, 819–857 (1988).

    Article CAS Google Scholar

  14. Goridis, C. & Brunet, J.-F. Semin. Cell Biol. 3, 189–197 (1992).

    Article CAS Google Scholar

  15. Theodosis, D. T., Rougon, G. & Poulain, D. A. Proc. natn. Acad. Sci. U.S.A. 88, 5494–5498 (1991).

    Article CAS ADS Google Scholar

  16. Seki, T. & Arai, Y. Neurosci. Res. 12, 503–513 (1991).

    Article CAS Google Scholar

  17. Morris, R. G. M. Learning Motivation 12, 239–260 (1981).

    Article Google Scholar

  18. Mansour, S. L., Thomas, K. R. & Capecci, M. R. Nature 336, 348–352 (1988).

    Article CAS ADS Google Scholar

  19. Goldowitz, D., Barthels, D., Lorenzon, N., Jungblut, A. & Wille, W. Devl Brain Res. 52, 151–160 (1990).

    Article CAS Google Scholar

  20. Zuber, C., Lackie, P. M., Catterall, W. A. & Roth, J. J. biol. Chem. 267, 9965–9971 (1992).

    CAS PubMed Google Scholar

  21. Thiel, G. Brain Path. 3, 87–95 (1993).

    Article CAS Google Scholar

  22. Rutishauser, U., Acheson, A., Hall, A. K., Mann, D. M. & Sunshine, J. Science 240, 53–57 (1988).

    Article CAS ADS Google Scholar

  23. Breipohl, W., Mackay-Sim, A., Grandt, D., Rehn, D. & Darrelmann, C. in Ontogeny of Olfaction (ed. Breipohl, W.) 21–34 (Springer, New York, 1986).

    Google Scholar

  24. Daniloff, J. K., Levi, G., Grumet, M., Rieger, F. & Edelman, G. M. J. Cell Biol. 103, 929–945 (1986).

    Article CAS Google Scholar

  25. Cornwell-Jones, C. Behavl Biol. 17, 131–137 (1976).

    Article Google Scholar

  26. Schorley, A. B., Rose, S. P. R., Zamani, M. R., Bock, E. & Schachner, M. Neuroscience 55, 499–509 (1993).

    Article Google Scholar

  27. Mayford, M., Barzilai, A., Keller, F., Schacher, S. & Kandel, E. R. Science 256, 638–649 (1992).

    Article CAS ADS Google Scholar

  28. Schenk, E. & Morris, R. G. M. Expl Brain Res. 58, 11–28 (1985).

    Article CAS Google Scholar

  29. Silva, A. J., Paylor, R., Wehner, J. & Tonegawa, S. Science 257, 206–211 (1992).

    Article CAS ADS Google Scholar

  30. Grant, S. G. N. et al. Science 258, 1903–1910 (1992).

    Article CAS ADS Google Scholar

Download references

Author information

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

Authors

  1. Harold Cremer

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  2. Rita Lange

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  3. Annette Christoph

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  4. Markus Plomann

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  5. Gaby Vopper

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  6. Jürgen Roes

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  7. Russell Brown

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  8. Stanley Baldwin

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  9. Philipp Kraemer

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  10. Stephen Scheff

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  11. Dagmar Barthels

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  12. Klaus Rajewsky

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  13. Wolfgang Wille

    View author publications

    You can also search for this author in PubMedGoogle Scholar

Rights and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/367455a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning (2024)
Top Articles
Latest Posts
Article information

Author: Kareem Mueller DO

Last Updated:

Views: 6209

Rating: 4.6 / 5 (66 voted)

Reviews: 89% of readers found this page helpful

Author information

Name: Kareem Mueller DO

Birthday: 1997-01-04

Address: Apt. 156 12935 Runolfsdottir Mission, Greenfort, MN 74384-6749

Phone: +16704982844747

Job: Corporate Administration Planner

Hobby: Mountain biking, Jewelry making, Stone skipping, Lacemaking, Knife making, Scrapbooking, Letterboxing

Introduction: My name is Kareem Mueller DO, I am a vivacious, super, thoughtful, excited, handsome, beautiful, combative person who loves writing and wants to share my knowledge and understanding with you.