Separation of VWF domain function using gene-targeted mic

使用基因靶向麦克风分离 VWF 结构域功能

• 批准号: 22591059
• 负责人: MATSUSHITA Tadashi
• 金额: $ 2.33万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591059/
• 关键词: 血友病; von Willebrand病; von Willebrand因子; 第VIII因子; ADAMTS13; von willebrand因子

von Willebrand factor is a multi-functional hemostatic factor that plays an important role of primary hemostasis. The VWF multi-function is accomplished by its multi-domain structure and each functional module may contribute to different hemostatic functions. We crossed VWFK1362A knock in mouse of which Lys1362, an important GPIb binding site, is mutated to Ala and VWF-/- mouse to yield the in vivo model of quantitative variations of functional/nonfunctional VWF models. We also introduced CAST/Ei background to increase the basic plasma VWF levels. VWFK1362A showed severe bleeding diathesis, suggesting VWF GPIb binding is pivotal function to maintain hemostasis. Crossing between VWFK1362A and VWF-/- mouse, however, was partially successful, because of infertility and prey. Further investigation would reveal quantitative function of VWF to maintain hemostasis in mammals.

血管性血友病因子是一种多功能止血因子，在原发性止血中起重要作用。VWF的多功能是通过其多结构域结构来实现的，每个功能模块都可能有不同的止血功能。我们将小鼠的VWFK1362A敲入，其中一个重要的GPIb结合位点Lys1362突变为Ala和VWF-/-小鼠，从而获得功能性/非功能性VWF模型的体内定量变化模型。我们还引入了CAST/Ei背景来提高基本的等离子体VWF水平。VWFK1362A表现出严重的出血特征，提示VWF与GPIb结合对维持止血具有关键作用。然而，由于不育和猎物，VWFK1362A与VWF-/-小鼠之间的杂交部分成功。进一步的研究将揭示VWF维持哺乳动物止血的定量功能。

项目成果

R702C mutation of the MYH9 gene causes great changes in blood cell and other organs in mice model

MYH9基因R702C突变导致小鼠模型血细胞和其他器官发生巨大变化

• 发表时间: 2011
• 作者: Honda H;Serada S;Fujimoto M;Hattori K;Ogata A;Nanki T;Takeuchi T;Naka T;Nobuaki Suzuki
• 通讯作者: Nobuaki Suzuki

消費性凝固傷害

消耗性凝血病

• 发表时间: 2010
• 期刊: 徹底ガイドDICのすべて-基礎と診療の最前線-救急・集中治療
• 作者: Aoki K;Ishiyama K;Itonaga H;Fukuda T;Taniguchi S;Ueda Y;Doki N;Sugio Y;Morishima Y;Nagamura T;Tanaka J;Atsuta Y;Ishikawa T;Miyazaki Y.;七島勉;松下正
• 通讯作者: 松下正

Severe hemophilia A in a Japanese female caused by an F8-intron 22 inversion associated with skewed X chromosome inactivation

• DOI: 10.1007/s12185-010-0659-9
• 发表时间: 2010-09-01
• 期刊: INTERNATIONAL JOURNAL OF HEMATOLOGY
• 影响因子: 2.1
• 作者: Miyawaki, Yuhri;Suzuki, Atsuo;Kojima, Tetsuhito
• 通讯作者: Kojima, Tetsuhito

A novel ENG mutation causing impaired co-translational processing of endoglin associated with hereditary hemorrhagic telangiestasia

一种新的 ENG 突变导致与遗传性出血性毛细血管扩张症相关的内皮糖蛋白共翻译加工受损

• DOI: 10.1016/j.thromres.2011.12.030
• 发表时间: 2012
• 期刊: Thrombosis Research
• 影响因子: 7.5
• 作者: J. Fujita;Y. Miyawaki;A. Suzuki;et al.;Atsuo Suzuki
• 通讯作者: Atsuo Suzuki

名古屋大学における血友病Bの血液凝固第IX因子遺伝子解析

名古屋大学血友病B的凝血因子IX基因分析

• 发表时间: 2012
• 作者: 村田 萌