Skip Navigation


Brain Advance Access originally published online on May 14, 2009
Brain 2009 132(10):2831-2838; doi:10.1093/brain/awp117
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
132/10/2831    most recent
awp117v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Hildebrandt, H.
Right arrow Articles by Gerardy-Schahn, R.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hildebrandt, H.
Right arrow Articles by Gerardy-Schahn, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Imbalance of neural cell adhesion molecule and polysialyltransferase alleles causes defective brain connectivity

Herbert Hildebrandt, Martina Mühlenhoff, Imke Oltmann-Norden*, Iris Röckle, Hannelore Burkhardt, Birgit Weinhold and Rita Gerardy-Schahn

Institute of Cellular Chemistry, OE 4330, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany

Correspondence to: Herbert Hildebrandt, Institute of Cellular Chemistry, OE 4330, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany E-mail: hildebrandt.herbert{at}mh-hannover.de

The neural cell adhesion molecule (NCAM) and its post-translational modification polysialic acid (polySia) are broadly implicated in neural development. Mice lacking the polysialyltransferases ST8SiaII and ST8SiaIV are devoid of polySia, and show severe malformation of major brain axon tracts. Here, we demonstrate how allelic variation of three interacting gene products (NCAM, ST8SiaII and ST8SiaIV) translates into various degrees of anterior commissure, corpus callosum and internal capsule hypoplasia. Loss of ST8SiaII alone caused mild, but distinct defects and the severity of the pathological phenotype found in mice lacking both polysialyltransferases could be stepwise attenuated by reducing NCAM expression. Analysis of mice with overall nine selected combinations of mutant NCAM and polysialyltransferase alleles revealed that the extent of the fibre tract deficiencies was not linked to the total amount of polySia or NCAM, but correlated strictly with the level of NCAM erroneously devoid of polySia during brain development. The defects implemented by the gain of polySia-free NCAM were reminiscent to abnormalities found in patients with schizophrenia. Since variations in NCAM1 and ST8SIA2 have been implicated in schizophrenia, these findings provide a mechanism how genetic interference with the complex coordination of NCAM polysialylation may lead to a neurodevelopmental predisposition to schizophrenia.

Key Words: polysialic acid; neural cell adhesion molecule; axon tract development; brain pathology; schizophrenia

.

Received February 13, 2009. Revised March 16, 2009. Accepted March 27, 2009.

*Present address: Fraunhofer Institut für Toxikologie und Experimentelle Medizin, Inhoffenstraße 7, 38124 Braunschweig, Germany


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.