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公开(公告)号：US20080044393A1
公开(公告)日：2008-02-21
申请号：US11050911
申请日：2005-02-04
CPC分类号： C07K14/4708 , A01K67/0275 , A01K67/0276 , A01K2217/05 , A01K2217/075 , A01K2227/105 , A01K2267/0306 , C12N15/8509 , C12N2830/008
摘要： Duchenne muscular dystrophy (DMD) is a progressive muscle disease that is caused by severe defects in the dystrophin gene and results in the patient's death by the third decade. The present invention utilizes the Double Mutant mice (DM) as an appropriate human model for DMD as these mice are deficient for both dystrophin and utrophin (mdx/+, utrn −/−), die at 3 months of age and suffer from severe muscle weakness, pronounced growth retardation, kyphosis, weight loss, slack posture, and immobility. Expression from a transgene of novel human retinal dystrophin Dp260 was shown to prevent premature death and reduce the severe muscular dystrophy phenotype to a mild clinical myopathy. Electromyography, histology, radiography, magnetic resonance imaging, and behavior studies concluded that DM transgenic mice grew normally, had normal spinal curvature and mobility, and had reduced muscle pathology. EMG and histologic data from transgenic DM mice showed decreased abnormalities to levels typical of mild myopathy, while the DM mice exhibited severe abnormalities commonly seen in human dystrophinopathies. The transgenic DM mice also had measurable movement levels comparable to those of untreated mdx mice and controls.
摘要翻译： Duchenne肌营养不良（DMD）是由肌营养不良蛋白基因的严重缺陷引起的进行性肌肉疾病，并导致患者在第三个十年内死亡。 本发明利用双重突变体小鼠（DM）作为DMD的合适人类模型，因为这些小鼠在肌营养不良蛋白和utrophin（mdx / +，utrn - / - ）中都是缺陷的，在3个月龄时死亡，并且患有严重的肌肉 虚弱，发育迟缓，驼背，体重减轻，松弛姿势和不动。 显示来自新型人视网膜肌营养不良蛋白Dp260的转基因的表达可预防过早死亡，并将严重的肌营养不良症表型降低至轻度临床肌病。 肌电图，组织学，放射成像，磁共振成像和行为研究得出结论，DM转基因小鼠正常生长，脊柱弯曲和移动性正常，肌肉病理学减少。 来自转基因DM小鼠的EMG和组织学数据显示轻度肌病典型的异常降低，而DM小鼠在人类肌营养不良症中常见的严重异常。 转基因小鼠也具有与未处理的mdx小鼠和对照相当的可测量运动水平。
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