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 language | English |
|---|---|
| Article number | 74 |
| Journal | Molecular brain |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 01-01-2014 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cellular and Molecular Neuroscience
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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 journal › Article
TY - JOUR
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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=84964697799&partnerID=8YFLogxK
U2 - 10.1186/s13041-014-0074-x
DO - 10.1186/s13041-014-0074-x
M3 - Article
C2 - 25298178
AN - SCOPUS:84964697799
VL - 7
JO - Molecular Brain
JF - Molecular Brain
SN - 1756-6606
IS - 1
M1 - 74
ER -