title: Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein knockout mice.
abstract: Calcium (Ca(2+)) influx through voltage-gated Ca(2+) channels (VGCCs) induces numerous intracellular events such as neuronal excitability, neurotransmitter release, synaptic plasticity, and gene regulation. It has been shown that genes related to Ca(2+) signaling, such as the CACNA1C, CACNB2, and CACNA1I genes that encode VGCC subunits, are associated with schizophrenia and other psychiatric disorders. Recently, VGCC beta-anchoring and -regulatory protein (BARP) was identified as a novel regulator of VGCC activity via the interaction of VGCC β subunits. To examine the role of the BARP in higher brain functions, we generated BARP knockout (KO) mice and conducted a comprehensive battery of behavioral tests. BARP KO mice exhibited greatly reduced locomotor activity, as evidenced by decreased vertical activity, stereotypic counts in the open field test, and activity level in the home cage, and longer latency to complete a session in spontaneous T-maze alteration test, which reached "study-wide significance." Acoustic startle response was also reduced in the mutants. Interestingly, they showed multiple behavioral phenotypes that are seemingly opposite to those seen in the mouse models of schizophrenia and its related disorders, including increased working memory, flexibility, prepulse inhibition, and social interaction, and decreased locomotor activity, though many of these phenotypes are statistically weak and require further replications. These results demonstrate that BARP is involved in the regulation of locomotor activity and, possibly, emotionality. The possibility was also suggested that BARP KO mice may serve as a unique tool for investigating the pathogenesis/pathophysiology of schizophrenia and related disorders. Further evaluation of the molecular and physiological phenotypes of the mutant mice would provide new insights into the role of BARP in higher brain functions.
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University Toyoake, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Nakao
authors.affiliation: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University Kyoto, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Miki
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University Toyoake, Japan ; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology Kawaguchi, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Shoji
authors.affiliation: Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University Kyoto, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishi
authors.affiliation: Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University Toyoake, Japan ; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology Kawaguchi, Japan ; Section of Behavior Patterns, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences Okazaki, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.affiliation: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University Kyoto, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
keywords: behavior; knockout mouse; psychiatric disorders; voltage-gated calcium channel beta-anchoring and -regulatory protein; voltage-gated calcium channels