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
N1 - Publisher Copyright:
© 2014 Shintani et al.
PY - 2014
Y1 - 2014
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.
KW - Behavior
KW - DTNBP1
KW - Dysbindin
KW - Dystrobrevin binding protein 1
KW - Immediate-early gene
KW - Methamphetamine
KW - Phencyclidine
KW - Psychiatric disorder
KW - Schizophrenia
KW - Transgenic mice
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U2 - 10.1186/s13041-014-0074-x
DO - 10.1186/s13041-014-0074-x
M3 - Article
C2 - 25298178
AN - SCOPUS:84964697799
SN - 1756-6606
VL - 7
JO - Molecular brain
JF - Molecular brain
IS - 1
M1 - 74
ER -