Behavioral characterization of mice overexpressing human dysbindin-1

Norihito Shintani, Yusuke Onaka, Ryota Hashimoto, Hironori Takamura, Tsuyoshi Nagata, Satomi Umeda-Yano, Akihiro Mouri, Takayoshi Mamiya, Ryota Haba, Shinsuke Matsuzaki, Taiichi Katayama, Hidenaga Yamamori, Takanobu Nakazawa, Kazuki Nagayasu, Yukio Ago, Yuki Yagasaki, Toshitaka Nabeshima, Masatoshi Takeda, Hitoshi Hashimoto

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Article number74
JournalMolecular brain
Volume7
Issue number1
DOIs
Publication statusPublished - 01-01-2014
Externally publishedYes

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Schizophrenia
Genes
Neuronal Plasticity
Immediate-Early Genes
Methamphetamine
Prefrontal Cortex
Transgenic Mice
Neurotransmitter Agents
Psychiatry
Carrier Proteins
Extremities
Phenotype
Neurons
Injections
Membranes
Brain
Therapeutics
dystrobrevin

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Shintani, N., Onaka, Y., Hashimoto, R., Takamura, H., Nagata, T., Umeda-Yano, S., ... Hashimoto, H. (2014). Behavioral characterization of mice overexpressing human dysbindin-1. Molecular brain, 7(1), [74]. https://doi.org/10.1186/s13041-014-0074-x
Shintani, Norihito ; Onaka, Yusuke ; Hashimoto, Ryota ; Takamura, Hironori ; Nagata, Tsuyoshi ; Umeda-Yano, Satomi ; Mouri, Akihiro ; Mamiya, Takayoshi ; Haba, Ryota ; Matsuzaki, Shinsuke ; Katayama, Taiichi ; Yamamori, Hidenaga ; Nakazawa, Takanobu ; Nagayasu, Kazuki ; Ago, Yukio ; Yagasaki, Yuki ; Nabeshima, Toshitaka ; Takeda, Masatoshi ; Hashimoto, Hitoshi. / Behavioral characterization of mice overexpressing human dysbindin-1. In: Molecular brain. 2014 ; Vol. 7, No. 1.
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Shintani, N, Onaka, Y, Hashimoto, R, Takamura, H, Nagata, T, Umeda-Yano, S, Mouri, A, Mamiya, T, Haba, R, Matsuzaki, S, Katayama, T, Yamamori, H, Nakazawa, T, Nagayasu, K, Ago, Y, Yagasaki, Y, Nabeshima, T, Takeda, M & Hashimoto, H 2014, 'Behavioral characterization of mice overexpressing human dysbindin-1', Molecular brain, vol. 7, no. 1, 74. https://doi.org/10.1186/s13041-014-0074-x

Behavioral characterization of mice overexpressing human dysbindin-1. / Shintani, Norihito; Onaka, Yusuke; Hashimoto, Ryota; Takamura, Hironori; Nagata, Tsuyoshi; Umeda-Yano, Satomi; Mouri, Akihiro; Mamiya, Takayoshi; Haba, Ryota; Matsuzaki, Shinsuke; Katayama, Taiichi; Yamamori, Hidenaga; Nakazawa, Takanobu; Nagayasu, Kazuki; Ago, Yukio; Yagasaki, Yuki; Nabeshima, Toshitaka; Takeda, Masatoshi; Hashimoto, Hitoshi.

In: Molecular brain, Vol. 7, No. 1, 74, 01.01.2014.

Research output: Contribution to journalArticle

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T1 - Behavioral characterization of mice overexpressing human dysbindin-1

AU - Shintani, Norihito

AU - Onaka, Yusuke

AU - Hashimoto, Ryota

AU - Takamura, Hironori

AU - Nagata, Tsuyoshi

AU - Umeda-Yano, Satomi

AU - Mouri, Akihiro

AU - Mamiya, Takayoshi

AU - Haba, Ryota

AU - Matsuzaki, Shinsuke

AU - Katayama, Taiichi

AU - Yamamori, Hidenaga

AU - Nakazawa, Takanobu

AU - Nagayasu, Kazuki

AU - Ago, Yukio

AU - Yagasaki, Yuki

AU - Nabeshima, Toshitaka

AU - Takeda, Masatoshi

AU - Hashimoto, Hitoshi

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

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Shintani N, Onaka Y, Hashimoto R, Takamura H, Nagata T, Umeda-Yano S et al. Behavioral characterization of mice overexpressing human dysbindin-1. Molecular brain. 2014 Jan 1;7(1). 74. https://doi.org/10.1186/s13041-014-0074-x