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

全基因组关联研究鉴定的RNF213基因的功能分析

• 批准号: 23390267
• 负责人: KURE Shigeo
• 金额: $ 12.56万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390267/
• 关键词: 小児神経学; モヤモヤ病; 疾患感受性遺伝子; RNF213遺伝子; 血管内皮細胞; 内頚動脈結紮; ノックアウト・マウス; 発症機序

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.

烟雾病（MMD）表现为进行性双侧颈内动脉狭窄和异常侧支血管。进行了全基因组关联研究，结果显示染色体17 q25-ter中的RNF 213基因座与MMD风险存在强关联。RNF 213的突变分析显示，在73%的非家族性MMD病例和1.4%的对照中存在创始者突变;该突变的携带者患MMD的风险增加。为了了解RNF 213基因的功能，我们采用基因打靶的方法建立了RNF 213基因敲除小鼠模型。纯合子小鼠出生和生长正常，脑血管发育未见异常。结扎颈内动脉，观察血管壁反应性肥大。纯合子小鼠无内膜细胞反应性增生，而野生型小鼠则无反应性增生，提示Rnf 213基因在内膜细胞增殖中起作用。

项目成果

Identification of a susceptibility gene for Moyamoya disease

烟雾病易感基因的鉴定

• 发表时间: 2013
• 作者: Morita M;Kuba K;Ichikawa A;Nakayama M;Katahira J;Iwamoto R;Watanebe T;Sakabe S;Daidoji T;Nakamura S;Kadowaki A;Ohto T;Nakanishi H;Taguchi R;Nakaya T;Murakami M;Yoneda Y;Arai H;Kawaoka Y;Penninger JM;Arita M;Imai Y.;Tsuyusaki Y;中屋隆明;Kure S.
• 通讯作者: Kure S.

Paradoxical increase in seizure frequency with valproate in nonketotic hyperglycinemia

非酮症高甘氨酸血症患者服用丙戊酸钠后癫痫发作频率反而增加

• DOI: 10.1016/j.braindev.2011.01.005
• 发表时间: 2012
• 期刊: Brain Dev
• 作者: Morita M;Kuba K;Ichikawa A;Nakayama M;Katahira J;Iwamoto R;Watanebe T;Sakabe S;Daidoji T;Nakamura S;Kadowaki A;Ohto T;Nakanishi H;Taguchi R;Nakaya T;Murakami M;Yoneda Y;Arai H;Kawaoka Y;Penninger JM;Arita M;Imai Y.;Tsuyusaki Y
• 通讯作者: Tsuyusaki Y

モヤモヤ病の疾患感受性遺伝子の同定

烟雾病易感基因的鉴定

• 发表时间: 2011
• 作者: Kure S;Kamada F;Aoki Y;Abe Y;Kikuchi A;Komatsuzaki S;Kanno J;Matsubara Y;Touho H;Miyatake S;Matsumoto N.;呉繁夫
• 通讯作者: 呉繁夫

Development of a de novo arteriovenous malformation after bilateral revascularization surgery in a child with moyamoya disease

烟雾病儿童双侧血运重建手术后出现新发动静脉畸形

• 发表时间: 2014
• 期刊: J Neurosurg Pediatr
• 作者: Fujimura M;Kimura N;Ezura M;Niizuma K;Uenohara H;Tominaga T.
• 通讯作者: Tominaga T.

Minocycline Prevents Focal Neurological Deterioration Due to Cerebral Hyperperfusion After Extracranial-Intracranial Bypass for Moyamoya Disease

• DOI: 10.1227/neu.0000000000000238
• 发表时间: 2014-02-01
• 期刊: NEUROSURGERY
• 影响因子: 4.8
• 作者: Fujimura, Miki;Niizuma, Kuniyasu;Tominaga, Teiji
• 通讯作者: Tominaga, Teiji