title: Mice lacking collapsin response mediator protein 1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition.
abstract: Collapsin response mediator protein 1 (CRMP1) is one of the CRMP family members that are involved in various aspects of neuronal development such as axonal guidance and neuronal migration. Here we provide evidence that crmp1 (-/-) mice exhibited behavioral abnormalities related to schizophrenia. The crmp1 (-/-) mice exhibited hyperactivity and/or impaired emotional behavioral phenotype. These mice also exhibited impaired context-dependent memory and long-term memory retention. Furthermore, crmp1 (-/-) mice exhibited decreased prepulse inhibition, and this phenotype was rescued by administration of chlorpromazine, a typical antipsychotic drug. In addition, in vivo microdialysis revealed that the methamphetamine-induced release of dopamine in prefrontal cortex was exaggerated in crmp1 (-/-) mice, suggesting that enhanced mesocortical dopaminergic transmission contributes to their hyperactivity phenotype. These observations suggest that impairment of CRMP1 function may be involved in the pathogenesis of schizophrenia. We propose that crmp1 (-/-) mouse may model endophenotypes present in this neuropsychiatric disorder.
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine Yokohama, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamashita
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine Yokohama, Japan.
authors.forename: Aoi
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Section of Behavior Patterns, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences Okazaki, Japan ; Genetic Engineering and Functional Genomics Group, Frontier Technology Center, Graduate School of Medicine, Kyoto University Kyoto, Japan ; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency Kawaguchi, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Takao
authors.affiliation: Laboratory of Molecular Psychopharmacology, Graduate School of Nanobiosciences, Yokohama City University Yokohama, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida Orlando, FL, USA.
authors.forename: Pappachan
authors.initials: P
authors.lastname: Kolattukudy
authors.affiliation: Section of Behavior Patterns, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences Okazaki, Japan ; Genetic Engineering and Functional Genomics Group, Frontier Technology Center, Graduate School of Medicine, Kyoto University Kyoto, Japan ; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency Kawaguchi, Japan ; Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University Toyoake, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine Yokohama, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
keywords: CRMP1; comprehensive behavioral test; hyperactivity; knockout mouse; mesocortical dopaminergic transmission; prepulse inhibition; schizophrenia