Functional analysis of RNF213 gene identified by genome-wide association study

点击翻译按钮获取中文摘要

Moyamoya disease (MMD) manifests progressive bilateral internal carotid artery stenosis and abnormal collateral vessels. A genome-wide association study was performed, which showed a strong association of RNF213 locus in chromosome 17q25-ter with MMD risk. Mutational analysis of RNF213 revealed a founder mutation in 73% of non-familial MMD cases and 1.4% of controls; carriers of this mutation have increased risk of MMD. We developed a genetic testing method for this founder mutation.To understand the function of RNF213 gene, we generated a knockout mice by gene targeting. Homozygous mice were born and grew normally and no abnormality was found in cerebral vascular development. The we ligated the internal carotid artery and observed reactive hypertrophy of vascular wall. The homozygous mice lacked the reactive hyperplasia of intima cells, which was constantly observed in wild-type mice, suggesting that Rnf213 gene plays a role in proliferation of intima cells.