title: Behavioral characterization of mice overexpressing human dysbindin-1.
abstract: BACKGROUND
  The dysbindin-1 gene (DTNBP1: dystrobrevin binding protein 1) is a promising schizophrenia susceptibility gene, known to localize almost exclusively to neurons in the brain, and participates in the regulation of neurotransmitter release, membrane-surface receptor expression, and synaptic plasticity. Sandy mice, with spontaneous Dtnbp1 deletion, display behavioral abnormalities relevant to symptoms of schizophrenia. However, it remains unknown if dysbindin-1 gain-of-function is beneficial or detrimental.
  
  
  RESULTS
  To answer this question and gain further insight into the pathophysiology and therapeutic potential of dysbindin-1, we developed transgenic mice expressing human DTNBP1 (Dys1A-Tg) and analyzed their behavioral phenotypes. Dys1A-Tg mice were born viable in the expected Mendelian ratios, apparently normal and fertile. Primary screening of behavior and function showed a marginal change in limb grasping in Dys1A-Tg mice. In addition, Dys1A-Tg mice exhibited increased hyperlocomotion after methamphetamine injection. Transcriptomic analysis identified several up- and down-regulated genes, including the immediate-early genes Arc and Egr2, in the prefrontal cortex of Dys1A-Tg mice.
  
  
  CONCLUSIONS
  The present findings in Dys1A-Tg mice support the role of dysbindin-1 in psychiatric disorders. The fact that either overexpression (Dys1A-Tg) or underexpression (Sandy) of dysbindin-1 leads to behavioral alterations in mice highlights the functional importance of dysbindin-1 in vivo.
authors.affiliation: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. shintani@phs.osaka-u.ac.jp.
authors.forename: Norihito
authors.initials: N
authors.lastname: Shintani
authors.affiliation: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. onaka@phs.osaka-u.ac.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Onaka
authors.affiliation: Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. hashimor@psy.med.osaka-u.ac.jp.|Department of Psychiatry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. hashimor@psy.med.osaka-u.ac.jp.
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. takamura@ugscd.osaka-u.ac.jp.
authors.forename: Hironori
authors.initials: H
authors.lastname: Takamura
authors.affiliation: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. t.nagata718@gmail.com.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nagata
authors.affiliation: Department of Molecular Neuropsychiatry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. umeda@mnp.med.osaka-u.ac.jp.
authors.forename: Satomi
authors.initials: S
authors.lastname: Umeda-Yano
authors.affiliation: Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, 468-8503, Japan. amouri@meijo-u.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Mouri
authors.affiliation: Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, 468-8503, Japan. mamiya@meijo-u.ac.jp.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Mamiya
authors.affiliation: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. ryota.haba@fujifilm.com.
authors.forename: Ryota
authors.initials: R
authors.lastname: Haba
authors.affiliation: Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. matsuzaki@ugscd.osaka-u.ac.jp.|Molecular Brain Science, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. matsuzaki@ugscd.osaka-u.ac.jp.|Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. matsuzaki@ugscd.osaka-u.ac.jp.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Matsuzaki
authors.affiliation: Molecular Brain Science, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. katayama@ugscd.osaka-u.ac.jp.
authors.forename: Taiichi
authors.initials: T
authors.lastname: Katayama
authors.affiliation: Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. yamamori@mnp.med.osaka-u.ac.jp.|Department of Molecular Neuropsychiatry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. yamamori@mnp.med.osaka-u.ac.jp.
authors.forename: Hidenaga
authors.initials: H
authors.lastname: Yamamori
authors.affiliation: iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. nakazawa@phs.osaka-u.ac.jp.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Nakazawa
authors.affiliation: iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. knagayasu@phs.osaka-u.ac.jp.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nagayasu
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. YAgo@mednet.ucla.edu.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ago
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashicho, Kodaira, Tokyo, 187-8502, Japan. yagasaki@research.twmu.ac.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yagasaki
authors.affiliation: Department of Regional Pharmaceutical Care & Sciences, Graduate School of Pharmaceutical Sciences, Meijo University, 150 Yagotoyama, Tenpaku-ku, Nagoya, 468-8503, Japan. tnabeshi@ccalumni.meijo-u.ac.jp.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
authors.affiliation: Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. mtakeda@psy.med.osaka-u.ac.jp.|Department of Psychiatry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. mtakeda@psy.med.osaka-u.ac.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. hasimoto@phs.osaka-u.ac.jp.|Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. hasimoto@phs.osaka-u.ac.jp.|iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. hasimoto@phs.osaka-u.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008694:Methamphetamine / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010622:Phencyclidine / Q000494:pharmacology
chemical_list: C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D008694:Methamphetamine; D010622:Phencyclidine