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脆性X智力低下蛋白1基因敲除斑马鱼表现出社会行为的早熟。

Fragile X Mental Retardation-1 Knockout Zebrafish Shows Precocious Development in Social Behavior.

作者信息

Wu Yao-Ju, Hsu Mao-Ting, Ng Ming-Chong, Amstislavskaya Tamara G, Tikhonova Maria A, Yang Yi-Ling, Lu Kwok-Tung

机构信息

1 Department of Life Science, National Taiwan Normal University , Taipei, Taiwan .

2 Center for General Education, National Quemoy University , Quemoy, Taiwan .

出版信息

Zebrafish. 2017 Oct;14(5):438-443. doi: 10.1089/zeb.2017.1446. Epub 2017 Aug 22.

DOI:10.1089/zeb.2017.1446
PMID:28829283
Abstract

Fragile X syndrome (FXS) is a generally hereditary form of human mental retardation that is caused by triplet repeat expansion (CGG) mutation in fragile X mental retardation 1 (fmr1) gene promoter and that results in the absence of the fragile X mental retardation protein (FMRP) expression. The common symptoms of FXS patients include learning disabilities, anxiety, autistic behaviors, as well as other behavioral abnormalities. Our previous results demonstrated the behavioral abnormalities in fmr1 knockout (KO) zebrafish such as fear memory impairment and autism-like behavior. Here, we studied the functional role of fmr1 gene on the development of social behavior by behavioral experiments, including shoaling behavior, shoaling preference, light/dark test, and novel tank task. Our results demonstrated that precocious development of shoaling behavior is found in fmr1 KO zebrafish without affecting the shoaling preference on conspecific zebrafish. The shoaling behavior appeared after 14 days postfertilization (dpf), and the level of shoaling elevated in fmr1 KO zebrafish. Furthermore, the fmr1 KO zebrafish at 28 dpf expressed higher anxiety level in novel tank task. These results suggest that the change of shoaling behavior in fmr1 KO zebrafish may result from hyperactivity and an increase of anxiety.

摘要

脆性X综合征(FXS)是一种常见的遗传性人类智力障碍形式,由脆性X智力低下1(fmr1)基因启动子中的三联体重复扩增(CGG)突变引起,导致脆性X智力低下蛋白(FMRP)表达缺失。FXS患者的常见症状包括学习障碍、焦虑、自闭症行为以及其他行为异常。我们之前的结果表明,fmr1基因敲除(KO)斑马鱼存在行为异常,如恐惧记忆受损和自闭症样行为。在此,我们通过行为实验研究了fmr1基因在社交行为发展中的功能作用,包括群居行为、群居偏好、明暗测试和新水箱任务。我们的结果表明,fmr1 KO斑马鱼的群居行为早熟,且不影响对同种斑马鱼的群居偏好。群居行为在受精后14天(dpf)出现,fmr1 KO斑马鱼的群居水平升高。此外,28 dpf的fmr1 KO斑马鱼在新水箱任务中表现出更高的焦虑水平。这些结果表明,fmr1 KO斑马鱼群居行为的改变可能是由多动和焦虑增加所致。

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