Lin S, Gaschen F, Burgunder J M
Department of Neurology, Faculty of Medicie, University of Berne, Switzerland.
J Neuropathol Exp Neurol. 1998 Aug;57(8):780-90. doi: 10.1097/00005072-199808000-00007.
Utrophin, an autosomal homologue of dystrophin, has been suggested as a possible therapeutic replacement of dystrophin in Duchenne or Becker muscular dystrophies (DMD/BMD). We have undertaken this study to examine the expression of utrophin in the skeletal muscle of dystrophin-deficient cats, a spontaneous animal model for dystrophinopathy. Dystrophin was normal in size, but very low in quantity by immunohistochemistry and Western blot. Utrophin was heterogeneously overexpressed at extrajunctional sarcolemma of regenerating muscle fibers, as defined by overexpression of the myogenic markers: vimentin, desmin, and developmental isoform of myosin heavy chain (MHCd). Muscle regeneration occurred in 6 stages as assessed by fiber size, and immunolabeling of desmin, vimentin, and MHCd. Differential developmental patterns of utrophin, alpha-sarcoglycan, and beta-dystroglycan expression were seen with an increase followed by a decrease and with changes in their respective location. These results suggest that utrophin is a regeneration-associated protein. It can functionally replace dystrophin in anchoring dystrophin-associated proteins (DAPs). However, the expression of utrophin and its anchored DAPs is restricted to the period of muscle regeneration and tends to decrease in late stages. This study therefore suggests a novel role of utrophin during skeletal muscle regeneration.
抗肌萎缩蛋白的常染色体同源物——肌养蛋白，被认为可能是杜兴氏或贝克氏肌营养不良症（DMD/BMD）中抗肌萎缩蛋白的治疗性替代物。我们开展了这项研究，以检测肌养蛋白在抗肌萎缩蛋白缺陷猫骨骼肌中的表达，该猫是抗肌萎缩蛋白病的自发性动物模型。通过免疫组织化学和蛋白质印迹法检测发现，抗肌萎缩蛋白大小正常，但数量极低。肌养蛋白在再生肌纤维的肌膜外节段呈异质性过表达，这由生肌标志物波形蛋白、结蛋白和肌球蛋白重链发育异构体（MHCd）的过表达来定义。根据纤维大小以及结蛋白、波形蛋白和MHCd的免疫标记评估，肌肉再生分为6个阶段。肌养蛋白、α-肌聚糖和β-肌营养不良聚糖的表达呈现出不同的发育模式，先是增加，随后减少，且各自的位置也发生了变化。这些结果表明，肌养蛋白是一种与再生相关的蛋白。它在锚定抗肌萎缩蛋白相关蛋白（DAPs）方面可在功能上替代抗肌萎缩蛋白。然而，肌养蛋白及其锚定的DAPs的表达仅限于肌肉再生期，且在后期趋于减少。因此，本研究揭示了肌养蛋白在骨骼肌再生过程中的新作用。
