Gramolini A O, Jasmin B J
Department of Physiology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Bioessays. 1997 Sep;19(9):747-50. doi: 10.1002/bies.950190903.
Although the precise function of utrophin at the postsynaptic membrane of the neuromuscular junction still remains unclear, despite recent genetic 'knockout' experiments, a separate study in a transgenic mouse model system for Duchenne muscular dystrophy (DMD) has nonetheless shown that overexpression of utrophin into extrasynaptic regions of muscle fibers can functionally compensate for the lack of dystrophin and alleviate the muscle pathology. In this context, the next step is to identify the mechanisms presiding over expression of utrophin at the neuromuscular synapse in attempts to induce its expression throughout DMD muscle fibers. In fact, additional studies have shown that an important DNA element contained with the utrophin promoter may confer synapse-specific expression to the utrophin gene. Identification of the events culminating in the transactivation of the utrophin gene within synaptic myonuclei should provide important cues for the development of an effective therapeutic strategy for DMD.
尽管经过最近的基因“敲除”实验，肌动蛋白在神经肌肉接头突触后膜的确切功能仍不清楚，但在杜兴氏肌营养不良症（DMD）的转基因小鼠模型系统中进行的另一项研究表明，将肌动蛋白过度表达于肌纤维的突触外区域能够在功能上补偿肌营养不良蛋白的缺失，并减轻肌肉病变。在此背景下，下一步是确定在神经肌肉突触处调控肌动蛋白表达的机制，以便在整个DMD肌纤维中诱导其表达。事实上，更多研究表明，肌动蛋白启动子中包含的一个重要DNA元件可能赋予肌动蛋白基因突触特异性表达。确定在突触肌细胞核内最终导致肌动蛋白基因反式激活的事件，应该能为开发有效的DMD治疗策略提供重要线索。
