Rett综合征相关基因MeCP2敲除大鼠模型的构建及分析

doi:10.16288/j.yczz.16-180

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Hereditas(Beijing) ›› 2016, Vol. 38 ›› Issue (11): 1004-1011.doi: 10.16288/j.yczz.16-180

• Research Articles • Previous Articles Next Articles

Generation and analysis of the Rett syndrome-associated MeCP2- null rat model

Wei Zhai, Hongxiu Hu, Liang Le, Fengfeng Zhuang, Kezhu Wang, Ying Zhao, Kai Wang, Xinmin Liu, Di’an Sun, Xiaoying Wang, Shihuan Kuang, Keping Hu

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China

Received:2016-05-18 Online:2016-11-20 Published:2016-08-26
Supported by:
[Supported by the National Natural Science Foundation of China(No.81271255)]

Abstract

Abstract: MeCP2 mutations are associated with the Rett syndrome (RTT). Currently, there is an urgent need for new animal models for RTT as the existing MeCP2 knockout mouse models fail to fully mimic the pathogenesis and symptoms of RTT patients. In order to investigate the role of MeCP2 in brain development and RTT pathogenesis, we aimed to set up the MeCP2-null rat model using the CRISPR/Cas9 technology. Firstly we constructed the MeCP2 targeting vector and then microinjected Cas9 mRNA and sgRNA mixtures into fertilized ova of SD rats. The sgRNA was designed to target the exon 2 of MeCP2. Next, knockout rats were confirmed using DNA sequencing and Western blotting. Lastly, phenotypes including growth and behaviors of MeCP2 knockout rats were analyzed. The results indicated that the MeCP2 knockout rats showed body weight loss, anxiety tendency and cognitive deficits. The MeCP2-null rat model established in this study recapitulates the major symptoms of RTT patients and provides an alternative tool for future studies of MeCP2 functions.

Key words: MeCP2, CRISPR/Cas9, SD rat model, Rett syndrome

Wei Zhai, Hongxiu Hu, Liang Le, Fengfeng Zhuang, Kezhu Wang, Ying Zhao, Kai Wang, Xinmin Liu, Di’an Sun, Xiaoying Wang, Shihuan Kuang, Keping Hu. Generation and analysis of the Rett syndrome-associated MeCP2- null rat model[J]. Hereditas(Beijing), 2016, 38(11): 1004-1011.

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Generation and analysis of the Rett syndrome-associated MeCP2- null rat model

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