title: Dorsal Forebrain-Specific Deficiency of Reelin-Dab1 Signal Causes Behavioral Abnormalities Related to Psychiatric Disorders.
abstract: Reelin-Dab1 signaling is involved in brain development and neuronal functions. The abnormalities in the signaling through either reduction of Reelin and Dab1 gene expressions or the genomic mutations in the brain have been reported to be associated with psychiatric disorders. However, it has not been clear if the deficiency in Reelin-Dab1 signaling is responsible for symptoms of the disorders. Here, to examine the function of Reelin-Dab1 signaling in the forebrain, we generated dorsal forebrain-specific Dab1 conditional knockout mouse (Dab1 cKO) and performed a behavioral test battery on the Dab1 cKO mice. Although conventional Dab1 null mutant mice exhibit cerebellar atrophy and cerebellar ataxia, the Dab1 cKO mice had normal cerebellum and showed no motor dysfunction. Dab1 cKO mice exhibited behavioral abnormalities, including hyperactivity, decreased anxiety-like behavior, and impairment of working memory, which are reminiscent of symptoms observed in patients with psychiatric disorders such as schizophrenia and bipolar disorder. These results suggest that deficiency of Reelin-Dab1 signal in the dorsal forebrain is involved in the pathogenesis of some symptoms of human psychiatric disorders.
authors.affiliation: Division of Developmental Neurobiology, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Imai
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake 470-1192, Japan.|Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Kawaguchi 332-0012, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Shoji
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ogata
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Kagawa
authors.affiliation: Department of Organ Anatomy, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Owada
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake 470-1192, Japan.|Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Kawaguchi 332-0012, Japan.|Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.affiliation: Division of Developmental Neurobiology, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Terashima
authors.affiliation: Division of Developmental Neurobiology, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.|Department of Organ Anatomy, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Katsuyama
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005239:Fear / Q000523:psychology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D046353:Immobility Response, Tonic / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000235:genetics; D001523:Mental Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D000091042:Reelin Protein; D013216:Reflex, Startle / Q000235:genetics; D012697:Serine Endopeptidases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
keywords: anxiety; behavioral test battery; conditional knockout; laminar structure