| 摘要 |
<p>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 (mdxl+, 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.</p> |
