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 journalArticlepeer-review

13 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 - 2014

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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