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

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

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

Weidong Li,Yu Zhou,J David Jentsch,Robert A M Brown,Xiaoli Tian,Dan Ehninger,William Hennah,Leena Peltonen,Jouko ,Matti O Huttunen,Jaakko Kaprio,Joshua T Trachtenberg,Alcino J Silva,Tyrone D Cannon,Weidong Li,Yu Zhou,J David Jentsch,Robert A M Brown,Xiaoli Tian,Dan Ehninger,William Hennah,Leena Peltonen,Jouko ,Matti O Huttunen,Jaakko Kaprio,Joshua T Trachtenberg,Alcino J Silva,Tyrone D Cannon,

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.

Specific developmental disruption of disrupted-in-schizophrenia-1 function results in schizophrenia-related phenotypes in mice. Publishing Authors By Initials

W Li,Y Zhou,JD Jentsch,RA Brown,X Tian,D Ehninger,W Hennah,L Peltonen,J ,MO Huttunen,J Kaprio,JT Trachtenberg,AJ Silva,TD Cannon,W Li,Y Zhou,JD Jentsch,RA Brown,X Tian,D Ehninger,W Hennah,L Peltonen,J ,MO Huttunen,J Kaprio,JT Trachtenberg,AJ Silva,TD Cannon,

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

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 18280-5

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 1091-6490

DAY: 2

MONTH: 11

YEAR: 2007

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

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LANGUAGE: eng

NlmUniqueID: 7505876

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Grant and Affiliation Information for Specific developmental disruption of disrupted-in-schizophrenia-1 function results in schizophrenia-related phenotypes in mice.

AFFILIATION: Department of Neurobiology, Semel Institute, Brain Research Institute, and Department of Urology, University of California, Los Angeles, CA 90095, USA.

Country: United States

AGENCY: United States NIMH

GRANT: MH52857

ACRONYM: MH

MEDLINETA: Proc Natl Acad Sci U S A

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