Nonaka I
National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Lab Anim Sci. 1998 Feb;48(1):8-17.
Recent advances in molecular biology have indicated that many mutant animal models of muscular dystrophy share common genetic and protein abnormalities similar to those of the human disease. The best example is a model of Duchenne muscular dystrophy (DMD), the mdx mouse. Similar to dystrophic muscle in DMD patients, dystrophin protein is not expressed along the surface membrane, even though the mdx mouse has no apparent signs of muscular dysfunction. Because clinical and pathologic findings in the dystrophic (mxd) dog are similar to those in DMD patients, it also has been regarded as a good model for therapeutic trials. The best known and most extensively studied dy+dy+ mouse lacks merosin (laminin alpha2), which is one subunit of a basement membrane protein, laminin. Because approximately half of all patients with the classical form of congenital muscular dystrophy also lack merosin, availability of this animal has revived interest in the study of the pathologic mechanism of fiber necrosis resulting from this membrane defect. The dystrophic hamster is a model of limb-girdle muscular dystrophy with sarcoglycan deficiency in which one of the dystrophin-associated glycoproteins, delta-sarcoglycan, is defective. Because these animal models have common protein and genetic defects similar to those seen in people with muscular dystrophies, they have been widely used to examine the effectiveness of gene therapy and the administration of pharmacologic and trophic factors.
分子生物学的最新进展表明，许多肌肉萎缩症的突变动物模型具有与人类疾病相似的常见遗传和蛋白质异常。最好的例子是杜氏肌营养不良症（DMD）的模型——mdx小鼠。与DMD患者的营养不良性肌肉相似，尽管mdx小鼠没有明显的肌肉功能障碍迹象，但肌营养不良蛋白在表面膜上并不表达。由于营养不良性（mxd）犬的临床和病理表现与DMD患者相似，它也被视为治疗试验的良好模型。最著名且研究最广泛的dy+dy+小鼠缺乏巢蛋白（层粘连蛋白α2），巢蛋白是基底膜蛋白层粘连蛋白的一个亚基。因为大约一半的经典型先天性肌营养不良症患者也缺乏巢蛋白，这种动物的出现重新激发了人们对研究这种膜缺陷导致纤维坏死病理机制的兴趣。营养不良性仓鼠是一种伴有肌聚糖缺乏的肢带型肌营养不良症模型，其中一种与肌营养不良蛋白相关的糖蛋白——δ-肌聚糖存在缺陷。由于这些动物模型具有与肌肉萎缩症患者相似的常见蛋白质和遗传缺陷，它们已被广泛用于检验基因治疗以及药理和营养因子给药的有效性。
