title: Generation and analysis of the Rett syndrome-associated MeCP2- null rat model.
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.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhai
authors.forename: Hong-xiu
authors.initials: HX
authors.lastname: Hu
authors.forename: Liang
authors.initials: L
authors.lastname: Le
authors.forename: Feng-feng
authors.initials: FF
authors.lastname: Zhuang
authors.forename: Ke-zhu
authors.initials: KZ
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Xin-min
authors.initials: XM
authors.lastname: Liu
authors.forename: Di’an
authors.initials: D
authors.lastname: Sun
authors.forename: Xiao-ying
authors.initials: XY
authors.lastname: Wang
authors.forename: Shi-huan
authors.initials: SH
authors.lastname: Kuang
authors.forename: Ke-ping
authors.initials: KP
authors.lastname: Hu
mesh_terms: D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D015518:Rett Syndrome / Q000235:genetics* / Q000378:metabolism
chemical_list: C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2