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

WWP1基因被认为是鸡肌肉萎缩症的一个有希望的候选基因，它编码E3泛素蛋白连接酶。营养不良鸡在基因上有一个错义突变，导致分子中的一个氨基酸发生变化。为了深入了解肌营养不良的分子机制，我们产生了表达与肌营养不良鸡相同的WWP1突变的转基因（Tg）小鼠。Tg小鼠后肢肌肉出现少量坏死和再生纤维。此外，衰老Tg小鼠常出现空泡。然而，尽管在营养不良的鸡中有报道，但在Tg肌肉中未发现α-异常糖基化。

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.