Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Neuregulin 1 and susceptibility to schizophrenia.

http://www.ncbi.nlm.nih.gov/pubmed/12145742

The cause of schizophrenia is unknown, but it has a significant genetic component. Pharmacologic studies, studies of gene expression in man, and studies of mouse mutants suggest involvement of glutamate and dopamine neurotransmitter systems. However, so far, strong association has not been found between schizophrenia and variants of the genes encoding components of these systems. Here, we report the results of a genomewide scan of schizophrenia families in Iceland; these results support previous work, done in five populations, showing that schizophrenia maps to chromosome 8p. Extensive fine-mapping of the 8p locus and haplotype-association analysis, supplemented by a transmission/disequilibrium test, identifies neuregulin 1 (NRG1) as a candidate gene for schizophrenia. NRG1 is expressed at central nervous system synapses and has a clear role in the expression and activation of neurotransmitter receptors, including glutamate receptors. Mutant mice heterozygous for either NRG1 or its receptor, ErbB4, show a behavioral phenotype that overlaps with mouse models for schizophrenia. Furthermore, NRG1 hypomorphs have fewer functional NMDA receptors than wild-type mice. We also demonstrate that the behavioral phenotypes of the NRG1 hypomorphs are partially reversible with clozapine, an atypical antipsychotic drug used to treat schizophrenia.

Pubmed ID: 12145742 RIS Download

Mesh terms: Animals | Chromosome Mapping | Chromosomes, Human, Pair 8 | Disease Models, Animal | Female | Genetic Predisposition to Disease | Haplotypes | Humans | Male | Mice | Mice, Inbred C57BL | Molecular Sequence Data | Neuregulin-1 | Receptor, Epidermal Growth Factor | Receptor, ErbB-4 | Schizophrenia

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

None

Comparative Toxicogenomics Database (Data, Disease Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.