血管生成素丧失突变在肌萎缩性脊髓侧索硬化症。
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吴D, Yu W, Kishikawa H, Folkerth RD, Iafrate AJ,沈Y,鑫W,西姆斯K,胡锦涛的女朋友
血管生成素丧失突变在肌萎缩性脊髓侧索硬化症。
安神经。2007年12月,62(6):609 - 17所示。
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17886298 (在PubMed]
- 文摘
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摘要目的:杂合的错义突变的编码区血管生成素(ANG),血管生成核糖核酸酶,在肌萎缩性脊髓侧索硬化症(ALS)已报告的病人。然而,在运动神经元的作用和生理和这些突变的功能的影响是未知的。我们寻必威国际app找新的突变并试图定义这些突变的功能结果。方法:我们测序的编码区和在一个独立的北美ALS患者。识别和突变特征然后使用功能化验的血管生成,ribonucleolysis,核易位。我们还研究了表达和正常人类的胎儿和成人脊髓。结果:我们发现四个突变的编码区和从298年ALS患者。三个突变出现在成熟的蛋白质。在四个突变,P(4)年代,S28N,和P112L小说,K17I报道。功能分析表明,这些和突变导致功能完全丧失。 The mutant ANG proteins are unable to induce angiogenesis because of a deficiency in ribonuclease activity, nuclear translocation, or both. As a correlate, we demonstrate strong ANG expression in both endothelial cells and motor neurons of normal human spinal cords from the developing fetus and adult. INTERPRETATION: We provide the first evidence that ANG mutations, identified in ALS patients, are associated with functional loss of ANG activity. Moreover, strong ANG expression, in normal human fetal and adult spinal cord neurons and endothelial cells, confirms the plausibility of ANG dysfunction being relevant to the pathogenesis of ALS.