文章基本信息

标题：Forebrain overexpression of CK1δ leads to down-regulation of dopamine receptors and altered locomotor activity reminiscent of ADHD
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作者：Mingming Zhou ; Heike Rebholz ; Christine Brocia 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：9
页码：4401-4406
DOI：10.1073/pnas.0915173107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Dopamine neurotransmission controls motor and perseverative behavior, is mediated by protein phosphorylation, and may be perturbed in disorders of attention and hyperactivity. To assess the role of casein kinase I (CK1) in the regulation of dopamine signaling, we generated a genetically modified mouse line that overexpresses CK1{delta} (CK1{delta} OE) specifically in the forebrain. Overexpression was confirmed both at the mRNA and at the protein levels. Under basal conditions, CK1{delta} OE mice exhibited horizontal and vertical hyperactivity, reduced anxiety, and nesting behavior deficiencies. The CK1{delta} OE mice also presented paradoxical responses to dopamine receptor stimulation, showing hypoactivity following injection of d-amphetamine or methylphenidate, indicating that CK1 activity has a profound effect on dopamine signaling in vivo. Interestingly, CK1{delta} overexpression led to significantly reduced D1R and D2R dopamine receptor levels. All together, under basal conditions and in response to drug stimulation, the behavioral phenotype of CK1{delta} OE mice is reminiscent of the symptoms and drug responses observed in attention-deficit/hyperactivity disorder and therefore the CK1{delta} OE mice appear to be a model for this disorder.
关键词：CK1 ; D1R ; methylphenidate ; protein kinase amphetamine