Porter J D, Merriam A P, Hack A A, Andrade F H, McNally E M
Department of Ophthalmology, Case Western Reserve University and The Research Institute of University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106-5068, USA.
Neuromuscul Disord. 2001 Mar;11(2):197-207. doi: 10.1016/s0960-8966(00)00171-1.
Models of the dystrophin-glycoprotein complex do not reconcile the novel sparing of extraocular muscle in muscular dystrophy. Extraocular muscle sparing in Duchenne muscular dystrophy implies the existence of adaptive properties in these muscles that may extend protection to other neuromuscular diseases. We studied the extraocular muscle morphology and dystrophin-glycoprotein complex organization in murine targeted deletion of the gamma-sarcoglycan (gsg(-/-)) and delta-sarcoglycan (dsg(-/-)) genes, two models of autosomal recessive limb girdle muscular dystrophy. In contrast to limb and diaphragm, the principal extraocular muscles were intact in gsg(-/-) and dsg(-/-) mice. However, central nucleated, presumptive regenerative, fibers were seen in the accessory extraocular muscles (retractor bulbi, levator palpebrae superioris) of both strains. Skeletal muscles of gsg(-/-) mice exhibited in vivo Evans Blue dye permeability, while the principal extraocular muscles did not. Disruption of gamma-sarcoglycan produced secondary displacement of alpha- and beta-sarcoglycans in the extraocular muscles. The intensity of immunofluorescence for dystrophin and alpha- and beta-dystroglycan also appeared to be slightly reduced. Utrophin localization was unchanged. The finding that sarcoglycan disruption was insufficient to elicit alterations in extraocular muscle suggests that loss of mechanical stability and increased sarcolemmal permeability are not inevitable consequences of mutations that disrupt the dystrophin-glycoprotein complex organization and must be accounted for in models of muscular dystrophy.
肌营养不良蛋白 - 糖蛋白复合物模型无法解释肌肉营养不良中眼外肌的新的 spared 现象。杜氏肌营养不良症中眼外肌 spared 现象意味着这些肌肉存在适应性特性，这可能会为其他神经肌肉疾病提供保护。我们研究了γ - 肌聚糖（gsg(-/-)）和δ - 肌聚糖（dsg(-/-)）基因靶向缺失小鼠的眼外肌形态和肌营养不良蛋白 - 糖蛋白复合物组织，这是常染色体隐性肢带型肌营养不良症的两种模型。与肢体和膈肌不同，gsg(-/-)和dsg(-/-)小鼠的主要眼外肌是完整的。然而，在这两种品系的附属眼外肌（眼球退缩肌、上睑提肌）中都发现了中央有核的、推测为再生的纤维。gsg(-/-)小鼠的骨骼肌在体内表现出伊文思蓝染料通透性，而主要眼外肌则没有。γ - 肌聚糖的破坏导致眼外肌中α - 和β - 肌聚糖的继发性移位。肌营养不良蛋白以及α - 和β - 肌营养不良聚糖的免疫荧光强度似乎也略有降低。抗肌萎缩蛋白的定位没有变化。肌聚糖破坏不足以引起眼外肌改变这一发现表明，机械稳定性丧失和肌膜通透性增加并非破坏肌营养不良蛋白 - 糖蛋白复合物组织的突变的必然结果，在肌肉营养不良模型中必须对此加以考虑。
