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

TitleSpecific developmental disruption of disrupted-in-schizophrenia-1 function results in schizophrenia-related phenotypes in mice.
Publication TypeJournal Article
Year of Publication2007
AuthorsLi, W, Zhou Y, Jentsch DJ, Brown RAM, Tian X, Ehninger D, Hennah W, Peltonen L, Lönnqvist J, Huttunen MO, Kaprio J, Trachtenberg JT, Silva AJ, Cannon TD
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue46
Pagination18280-5
Date Published2007 Nov 13
ISSN1091-6490
KeywordsAnimals, Mice, Mice, Transgenic, Nerve Tissue Proteins, Phenotype
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.

DOI10.1111/j.1751-7893.2008.00088.x
Alternate JournalProc. Natl. Acad. Sci. U.S.A.