New pathomechanism and the application of the treatment for Fukuyama-type congenital muscular dystrophy

福山型先天性肌营养不良症新发病机制及治疗应用

• 批准号: 20790725
• 负责人: TANIGUCHI Mariko
• 金额: $ 2.75万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790725/
• 关键词: 先天生筋ジストロフィー; ゲノム創薬; スプライシング異常; アンチセンス治療; 福山型筋ジストロフィー; 遺伝子; 先天性筋ジストロフィー; RNA創薬

1, We revealed that FCMD is caused by splicing abnormality which is induced by pathogenic exon trapping of SVA retrotransposal insertion. 2, We also detected the abnormal fukutin protein in FCMD. 3, We checked that the same abnormal splicing pattern was seen in FCMD model mice. 4 We adopted phosphorothioate-linked 2'-O-methyl RNA (2'OMePS) and Morpholino oligonucleotides to design several 25 mer AONs to search the best target sequences.

1、我们发现FCMD是由SVA反转录酶插入的致病性外显子捕获引起的剪接异常引起的。2、在FCMD中也检测到异常的fukarin蛋白。3、在FCMD模型小鼠中发现了同样的异常剪接模式。4采用硫代磷酸连接的2 '-O-甲基RNA（2' OMePS）和Morpholino寡核苷酸设计了几个25 mer的AON，以寻找最佳靶序列。

项目成果

小児の症候群、cat eye症候群、Coffin-Siris症候群、Cohen症候群、小児科診療

小儿综合症、猫眼综合症、科芬-西里斯综合症、科恩综合症、儿科治疗

• 发表时间: 2009

Chromosomal instability mediated by non-B DNA: Cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans

• DOI: 10.1101/gr.079244.108
• 发表时间: 2009-02-01
• 期刊: GENOME RESEARCH
• 影响因子: 7
• 作者: Inagaki, Hidehito;Ohye, Tamae;Kurahashi, Hiroki
• 通讯作者: Kurahashi, Hiroki

Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy.

• DOI: 10.1093/hmg/ddn387
• 发表时间: 2009-02-15
• 期刊: Human molecular genetics
• 影响因子: 3.5
• 作者: Kanagawa M;Nishimoto A;Chiyonobu T;Takeda S;Miyagoe-Suzuki Y;Wang F;Fujikake N;Taniguchi M;Lu Z;Tachikawa M;Nagai Y;Tashiro F;Miyazaki J;Tajima Y;Takeda S;Endo T;Kobayashi K;Campbell KP;Toda T
• 通讯作者: Toda T

福山型先天性筋ジストロフィーはスプライシング病である

福山先天性肌营养不良症是一种剪接病

• 发表时间: 2010
• 作者: 谷口真理子;小林千浩;金川基;戸田 達史
• 通讯作者: 戸田 達史

Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model miceto dystfoilycanbpathy

在新型模型小鼠中，残余层粘连蛋白结合活性和 LARGE 增强的肌营养不良聚糖糖基化

• 发表时间: 2009
• 期刊: Human Molecular Genetics 18
• 作者: Inagaki;H.;Ohye;T.;Kogo;T.;Kato;T.;Bolor;H.;Taniguchi;M.;Shaikh;T.H.;Emanuel;B.S.;Kurahashi;H.;Kanagawa M;Inagaki H;Motoi Kanagawa
• 通讯作者: Motoi Kanagawa