Generation and characterization of transgenic mice expressing mutated WWP1 gene responsible for chicken muscular dystrophy

表达导致鸡肌营养不良症的突变WWP1基因的转基因小鼠的产生和表征

• 批准号: 21500384
• 负责人: IMAMURA Michihiro
• 金额: $ 2.91万
• 依托单位: National Center of Neurology and Psychiatry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21500384/
• 关键词: 酵素; 細胞組織; 遺伝子; 実験動物; 筋ジストロフィー

The WWP1 gene was identified as a promising candidate responsible for chicken muscular dystrophy, which encodes a E3 ubiquitin protein ligase. Dystrophy chicken has a missense mutation in the gene causes one amino acid change in the molecule. To gain insight into molecular mechanism of the muscular dystrophy, we generated transgenic(Tg) mice expressing the same mutated WWP1 as found in dystrophy chicken. Tg mice showed a small number of necrotic and regenerating fibers in the hind limb muscle. Moreover, vacuoles were often found in aged Tg mice. Whereas, aberrant glycosylation ofα-dystroglycan was not shown in Tg muscle despite of a report with dystrophy chicken.

WWP 1基因编码E3泛素蛋白连接酶，被认为是鸡肌营养不良症的潜在致病基因。营养不良鸡有一个基因的错义突变，导致分子中一个氨基酸的变化。为了深入了解肌营养不良症的分子机制，我们产生了转基因（Tg）小鼠，表达与营养不良鸡中发现的相同突变的WWP 1。Tg小鼠后肢肌肉中出现少量坏死和再生纤维。此外，空泡往往发现在老年Tg小鼠。然而，尽管有营养不良鸡的报道，但在Tg肌肉中未显示α-肌营养不良聚糖的异常糖基化。

项目成果

Analysis of Expression of WWP1 protein in Mouse Normal Tissues

小鼠正常组织中WWP1蛋白的表达分析

• 发表时间: 2011
• 作者: IMAMURA;Michihiro
• 通讯作者: Michihiro

Searching for loss of imprinting of theε-sarcoglycan gene in the cells of ε-sarcoglycan partial knockout mice

寻找ε-肌聚糖部分敲除小鼠细胞中ε-肌聚糖基因印记的丢失

• 发表时间: 2009
• 作者: Imamura M;Takeda S
• 通讯作者: Takeda S

Effect of a Point Mutation in the WWP1 Gene Associated with Chicken Muscular Dystrophy on Mouse Muscle Expressing Mutated WWP1 Transgene

与鸡肌营养不良症相关的 WWP1 基因点突变对表达突变 WWP1 转基因的小鼠肌肉的影响

• 发表时间: 2011
• 作者: IMAMURA;Michihiro;Hai-Yuan Yue;今村道博
• 通讯作者: 今村道博

Expression pattern of WWP1 in muscular dystrophic and normal chickens.

肌营养不良鸡和正常鸡中WWP1的表达模式。

• DOI: 10.2141/jpsa.46.95
• 发表时间: 2009
• 期刊: Journal of Poultry Science
• 影响因子: 1.5
• 作者: Hirokazu Matsumoto;Hideaki Maruse;S. Sasazaki;A. Fujiwara;S. Takeda;N. Ichihara;T. Kikuchi;F. Mukai;H. Mannen
• 通讯作者: H. Mannen

Generation of transgenic mouse expressing mutated wwp1 gene responsible for chicken muscular dystrophy.

表达导致鸡肌营养不良症的突变 wwp1 基因的转基因小鼠的产生。

• 发表时间: 2010
• 作者: Imamura M;Matsumoto H;Inaba Y;Mannen H;Takeda S
• 通讯作者: Takeda S