Specific developmental disruption of disrupted-in-schizophrenia-1 function results in schizophrenia-related phenotypes in mice.

Abstract

Disrupted-in-schizophrenia 1 (DISC1) was initially discovered through a balanced translocation (1;11)(q42.1;q14.3) that results in loss of the C terminus of the DISC1 protein, a region that is thought to play an important role in brain development. Here, we use an inducible and reversible transgenic system to demonstrate that early postnatal, but not adult induction, of a C-terminal portion of DISC1 in mice results in a cluster of schizophrenia-related phenotypes, including reduced hippocampal dendritic complexity, depressive-like traits, abnormal spatial working memory, and reduced sociability. Accordingly, we report that individuals in a discordant twin sample with a DISC1 haplotype, associating with schizophrenia as well as working memory impairments and reduced gray matter density, were more likely to show deficits in sociability than those without the haplotype. Our findings demonstrate that alterations in DISC1 function during brain development contribute to schizophrenia pathogenesis.

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@article{Li2007SpecificDD, title={Specific developmental disruption of disrupted-in-schizophrenia-1 function results in schizophrenia-related phenotypes in mice.}, author={Weidong Li and Yu Zhou and James David Jentsch and Robert A. Brown and Xiaoli Tian and Dan Ehninger and W. Hennah and Leena Peltonen and Jouko L{\"{o}nnqvist and Matti Huttunen and Jaakko Kaprio and Joshua T. Trachtenberg and Alcino J. Silva and Tyrone D. Cannon}, journal={Proceedings of the National Academy of Sciences of the United States of America}, year={2007}, volume={104 46}, pages={18280-5} }