title: Overexpression of G100S mutation in PRKAG2 causes Wolff-Parkinson-White syndrome in zebrafish.
abstract: The Wolff-Parkinson-White (WPW) syndrome was believed to be associated with PRKAG2 gene mutations. In this study, we verified the pathopoiesis of G100S mutation, a novel mutation only discovered in Chinese patients with WPW, in cardiac disorder. Similar to R302Q, when overexpressed PRKAG2 G100S mutant in zebrafish, we observed a thicker heart wall, detected a decreased AMPK enzymatic activity by tissue AMPK kinase activity colorimetric technique, as well as examined an increased glycogen storage in heart wall using the method for periodic acid-Schiff staining, in comparison with the zebrafish without exogenous PRKAG2 (mock) or with wild-type PRKAG2 (WT). Taken together, we concluded PRKAG2 G100S mutation might contribute to impair the AMP-activated protein kinase function, which resulted in increased cardiac glycogen storage, serving as a pathogenesis for WPW syndrome in Chinese.
authors.affiliation: Department of Cardiovascular Diseases, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: B L
authors.initials: BL
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Ye
authors.forename: R L
authors.initials: RL
authors.lastname: Xu
authors.forename: X H
authors.initials: XH
authors.lastname: You
authors.forename: Y W
authors.initials: YW
authors.lastname: Qin
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Cao
authors.forename: J L
authors.initials: JL
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Zheng
authors.forename: X X
authors.initials: XX
authors.lastname: Zhao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D005822:Genetic Vectors / Q000235:genetics; D006652:Histological Techniques; D006801:Humans; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense / Q000235:genetics*; D010503:Periodic Acid-Schiff Reaction; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes / Q000235:genetics; D014927:Wolff-Parkinson-White Syndrome / Q000235:genetics*; D015027:Zebrafish
chemical_list: C526223:PRKAG2 protein, human; D055372:AMP-Activated Protein Kinases
keywords: PRKAG2 cardiac; mutation; syndrome; zebrafish