Guo Dongsheng, Liu Haikun, Gao Ge, Ruzi Aynisahan, Wang Kepin, Wu Han, Lai Keyu, Liu Yanli, Yang Fan, Lai Liangxue, Li Yin-Xiong
Institute of Public Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Stem Cell Res. 2016 Nov;17(3):640-642. doi: 10.1016/j.scr.2016.11.011. Epub 2016 Nov 9.
The gene of ATP-binding cassette subfamily C member 8 (Abcc8) is cytogenetically located at 11p15.1 and encodes the sulfonylurea receptor (SUR1). SUR1 is a subunit of ATP-sensitive potassium channel (KAPT) in the β-cell regulating insulin secretion. Mutations of ABCC8 are responsible for congenital hyperinsulinism (CHI). Here we generated an Abcc8 homozygous mutant cell line by CRISPR/Cas9 technique with 22bp deletion resulting in abnormal splicing on human embryonic stem cell line H1. The phenotypic characteristics of this cell line reveal defective KATP channel and diazoxide-unresponsive that provides an ideal model for molecular pathology research and drug screening for CHI.
ATP结合盒亚家族C成员8（Abcc8）基因在细胞遗传学上定位于11p15.1，编码磺脲类受体（SUR1）。SUR1是β细胞中调节胰岛素分泌的ATP敏感性钾通道（KAPT）的一个亚基。ABCC8突变导致先天性高胰岛素血症（CHI）。在此，我们利用CRISPR/Cas9技术在人胚胎干细胞系H1中产生了一个Abcc8纯合突变细胞系，该细胞系有22bp缺失，导致剪接异常。该细胞系的表型特征显示ATP敏感性钾通道缺陷且对二氮嗪无反应，为CHI的分子病理学研究和药物筛选提供了理想模型。
