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Research Article

The involvement of ErbB4 with schizophrenia: Association and expression studies*

Gilad Silberberg

Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

This study is dedicated to my late beloved father, Moshe Haim Silberberg.Search for more papers by this author
Ariel Darvasi

Life Sciences Institute, the Hebrew University of Jerusalem, Jerusalem, Israel

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Ronit Pinkas‐Kramarski

Department of Neurobiochemistry. Tel‐Aviv University, Tel‐Aviv, Israel

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Ruth Navon

Corresponding Author

E-mail address:rnavon@post.tau.ac.il

Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
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First published: 09 January 2006
Cited by: 131
*

This study was presented at the Personalized Medicine Europe workshop in Tel Aviv, Israel on June 20, 2005, and at the World Congress on Psychiatric Genetics XIII in Boston, MA on October 17, 2005.

Abstract

Neuregulin 1 (NRG1) has been found to be associated with schizophrenia in several populations. Consistently, mutant mice heterozygous for either NRG1 or its receptor, ErbB4, show a behavioral phenotype that overlaps with mouse models for schizophrenia. These observations raised the hypothesis that impaired NRG1–ErbB4 signaling may contribute to schizophrenia susceptibility. Nineteen SNPs encompassing the ErbB4 gene were selected from the HapMap database and genotyped in genomic DNA isolated from 59 Ashkenazi schizophrenia patients and 130 matched controls. Expression analysis of ErbB4 splice variants was performed on postmortem DLPFC samples obtained from Caucasian patients and controls by real‐time PCR. We found a highly significant difference between patient and control groups in three SNPs from one linkage disequilibrium (LD) block both in allele (P = 0.013, 0.0045, 0.0049) and genotype frequencies (P = 0.00013, 0.000021, 0.00018), as well as a risk haplotype (P = 0.00044). Expression analysis indicated that the CYT‐1 isoform is overexpressed in patients (P = 0.047) and that juxtamembrane (JM)‐a displays a similar trend (P = 0.081). This study provides a direct link between ErbB4 and the disease. We propose that NRG1 and its receptor ErbB4 are components of a biological pathway, involved in the pathophysiology of schizophrenia. © 2006 Wiley‐Liss, Inc.

Number of times cited: 131

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