Overexpression of G100S mutation in PRKAG2 causes Wolff–Parkinson–White syndrome in zebrafish

Authors


  • Nothing to declare.

Corresponding authors: Xian-Xian Zhao, Department of Cardiovascular Diseases, Changhai Hospital, Second Military Medical University, No. 168 Changhai Road, Shanghai 200433, China.

Tel.: +86 21 3116 1255;

fax: +86 21 3116 1248;

e-mail: 13601713431@163.com

and

Xing Zheng, Department of Cardiovascular Diseases, Changhai Hospital, Second Military Medical University, No. 168 Changhai Road, Shanghai 200433, China.

Tel.: +86 21 3116 1255;

fax: +86 21 3116 1248;

e-mail: zhengxing57530@163.com

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.

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