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题名:	Mice lacking cyclin-dependent kinase-like 5 manifest autistic and ADHD-like behaviors
作者:	廖文霖 Jhang, Cian-Ling Huang, Tzyy-Nan Hsueh, Yi-Ping Liao, Wenlin
贡献者:	神科所
关键词:	dopamine;attention-deficit/hyperactivity disorder;autistic disorder;cyclins;phosphotransferases;mice
日期:	2017
上传时间:	2017-09-28 17:39:26 (UTC+8)
摘要:	Neurodevelopmental disorders frequently share common clinical features and appear high rate of comorbidity, such as those present in patients with attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). While characterizing behavioral phenotypes in the mouse model of cyclin-dependent kinase-like 5 (CDKL5) disorder, a neurodevelopmental disorder caused by mutations in the X-linked gene encoding CDKL5, we found that these mice manifested behavioral phenotypes mimicking multiple key features of ASD, such as impaired social interaction and communication, as well as increased stereotypic digging behaviors. These mice also displayed hyper-locomotion, increased aggressiveness and impulsivity, plus deficits in motor and associative learning, resembling primary symptoms of ADHD. Through brain region-specific biochemical analysis, we uncovered that loss of CDKL5 disrupts dopamine synthesis and the expression of social communication-related key genes, such as forkhead-box P2 and mu-opioid receptor, in the corticostriatal circuit. Together, our findings support that CDKL5 plays a role in the comorbid features of autism and ADHD, and mice lacking CDKL5 may serve as an animal model to study the molecular and circuit mechanisms underlying autism-ADHD comorbidity.
關聯:	Human Molecular Genetics
数据类型:	article
DOI 連結:	https://doi.org/10.1093/hmg/ddx279
DOI:	10.1093/hmg/ddx279
显示于类别:	[神經科學研究所 ] 期刊論文

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