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学科主题: 临床医学
题名:
RNAi-induced down-regulation of Mecp2 expression in the rat brain
作者: Jin, Jing; Bao, Xinhua; Wang, Hansen; Pan, Hong; Zhang, Yuzhi; Wu, Xiru
关键词: neonatal rat ; methyl-CpG-binding protein 2 ; brain ; lentiviral vector ; small hairpin RNA (shRNA) ; hippocampus ; cerebral cortex
刊名: INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
发表日期: 2008-08-01
DOI: 10.1016/j.ijdevneu.2008.02.009
卷: 26, 期:5, 页:457-465
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Developmental Biology ; Neurosciences
研究领域[WOS]: Developmental Biology ; Neurosciences & Neurology
关键词[WOS]: CPG-BINDING PROTEIN-2 ; RETT-SYNDROME ; MUTANT MICE ; IN-VIVO ; GENE ; INTERFERENCE ; MUTATIONS ; PHENOTYPE ; ELEGANS ; DISEASE
英文摘要:

The MECP2 (methyl-CpG-binding protein 2) gene has been implicated in the pathogenesis of Rett Syndrome. A rat model with a down-regulated Mecp2 was established using a recombinant lentiviral vector expressing small hairpin RNA of the rat Mecp2 gene. Four recombinant vectors were constructed by inserting sequences of small hairpin RNA targeting the rat Mecp2 gene. To determine which vector resulted in optimal down-regulation, rat skin fibroblasts were transfected with four recombinant vectors, respectively. The recombinant vector mecp2-sh-1 decreased expression of Mecp2 mRNA and protein relative to the Control group. 12-24 h after birth, neonatal rat pups were divided into three groups, Re-Lenti group (injected with recombinant lentiviral vector, mecp2-sh-1), Lenti group (injected with lentivirus containing no inserted sequences) and a non-injected Control group (Control group). Rats in the injection groups were given intraventricular injections. 7 days and 21 days following injection, no inflammation was observed in the rat brain in the two injected groups, whereas EGFP expression was readily detectable. Sensory-motor reflexes were transiently abnormal in Re-Lenti group, whereas no abnormality was observed in either Control group. Mecp2 mRNA was lower in the hippocampus and cerebral cortex in the Re-Lenti group relative to the Lenti and Control groups. Although no typical RTT like symptoms were observed, the neonatal rats injected with recombinant lentivirus displayed some transient neurobehavioral abnormalities during early development. Bdnf mRNA expression decreased in the hippocampus, supporting the hypothesis that Bdnf may be a target gene of MeCP2 in the CNS. (C) 2008 ISDN. Published by Elsevier Ltd. All rights reserved.

语种: 英语
WOS记录号: WOS:000256650900009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54817
Appears in Collections:北京大学第一临床医学院_儿科_期刊论文

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作者单位: Peking Univ, Dept Pediat, Hosp 1, Beijing 100034, Peoples R China

Recommended Citation:
Jin, Jing,Bao, Xinhua,Wang, Hansen,et al. RNAi-induced down-regulation of Mecp2 expression in the rat brain[J]. INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE,2008,26(5):457-465.
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