title: Behavioral alterations associated with targeted disruption of exons 2 and 3 of the Disc1 gene in the mouse.
abstract: Disrupted-In-Schizophrenia 1 (DISC1) is a promising candidate gene for susceptibility to psychiatric disorders, including schizophrenia. DISC1 appears to be involved in neurogenesis, neuronal migration, axon/dendrite formation and synapse formation; during these processes, DISC1 acts as a scaffold protein by interacting with various partners. However, the lack of Disc1 knockout mice and a well-characterized antibody to DISC1 has made it difficult to determine the exact role of DISC1 in vivo. In this study, we generated mice lacking exons 2 and 3 of the Disc1 gene and prepared specific antibodies to the N- and C-termini of DISC1. The Disc1 mutant mice are viable and fertile, and no gross phenotypes, such as disorganization of the brain's cytoarchitecture, were observed. Western blot analysis revealed that the DISC1-specific antibodies recognize a protein with an apparent molecular mass of ~100 kDa in brain extracts from wild-type mice but not in brain extracts from DISC1 mutant mice. Immunochemical studies demonstrated that DISC1 is mainly localized to the vicinity of the Golgi apparatus in hippocampal neurons and astrocytes. A deficiency of full-length Disc1 induced a threshold shift in the induction of long-term potentiation in the dentate gyrus. The Disc1 mutant mice displayed abnormal emotional behavior as assessed by the elevated plus-maze and cliff-avoidance tests, thereby suggesting that a deficiency of full-length DISC1 may result in lower anxiety and/or higher impulsivity. Based on these results, we suggest that full-length Disc1-deficient mice and DISC1-specific antibodies are powerful tools for dissecting the pathophysiological functions of DISC1.
authors: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors: Keisuke
authors: K
authors: Kuroda
authors: Shinnosuke
authors: S
authors: Yamada
authors: Motoki
authors: M
authors: Tanaka
authors: Michiro
authors: M
authors: Iizuka
authors: Hisashi
authors: H
authors: Yano
authors: Daisuke
authors: D
authors: Mori
authors: Daisuke
authors: D
authors: Tsuboi
authors: Tomoki
authors: T
authors: Nishioka
authors: Takashi
authors: T
authors: Namba
authors: Yukihiko
authors: Y
authors: Iizuka
authors: Shimpei
authors: S
authors: Kubota
authors: Taku
authors: T
authors: Nagai
authors: Daisuke
authors: D
authors: Ibi
authors: Rui
authors: R
authors: Wang
authors: Atsushi
authors: A
authors: Enomoto
authors: Mayu
authors: M
authors: Isotani-Sakakibara
authors: Naoya
authors: N
authors: Asai
authors: Kazushi
authors: K
authors: Kimura
authors: Hiroshi
authors: H
authors: Kiyonari
authors: Takaya
authors: T
authors: Abe
authors: Akira
authors: A
authors: Mizoguchi
authors: Masahiro
authors: M
authors: Sokabe
authors: Masahide
authors: M
authors: Takahashi
authors: Kiyofumi
authors: K
authors: Yamada
authors: Kozo
authors: K
authors: Kaibuchi
mesh_terms: D000375:Aging / Q000187:drug effects / Q000473:pathology; D000588:Amines / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology; D005091:Exons / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018390:Gene Targeting; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D007150:Immunohistochemistry; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000276:immunology; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
chemical_list: D000588:Amines; D000906:Antibodies; C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins; D003024:Clozapine