期刊
MOLECULAR BRAIN
卷 7, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s13041-014-0074-x
关键词
Dysbindin; DTNBP1; Dystrobrevin binding protein 1; Psychiatric disorder; Schizophrenia; Transgenic mice; Behavior; Methamphetamine; Phencyclidine; Immediate-early gene
资金
- Japan Society for the Promotion of Science [23790086, 22390225, 23659565, 25293250, 26293020, 26670122]
- Funding Program for Next Generation World-Leading Researchers [LS081]
- Uehara Memorial Foundation, Japan
- Grants-in-Aid for Scientific Research [26670541, 221S0003, 24590304, 23790086, 25640033, 26670122, 25293250, 26860055, 25461730] Funding Source: KAKEN
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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