title: 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.
authors.affiliation: Department of Neurobiology, Semel Institute, Brain Research Institute, and Department of Urology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: J David
authors.initials: JD
authors.lastname: Jentsch
authors.forename: Robert A M
authors.initials: RA
authors.lastname: Brown
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Tian
authors.forename: Dan
authors.initials: D
authors.lastname: Ehninger
authors.forename: William
authors.initials: W
authors.lastname: Hennah
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Jouko
authors.initials: J
authors.lastname: Lönnqvist
authors.forename: Matti O
authors.initials: MO
authors.lastname: Huttunen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Trachtenberg
authors.forename: Alcino J
authors.initials: AJ
authors.lastname: Silva
authors.forename: Tyrone D
authors.initials: TD
authors.lastname: Cannon
mesh_terms: D000818:Animals; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype
chemical_list: C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins