RT期刊文章SR电子T1小说RMND1敲入小鼠概括临床和生化异常患者中观察到乔(P3.329)摩根富林明神经病学神经病学FD Lippincott Williams &威尔金斯SP P3.329 VO 90 15补充A1玛丽亚j . SANCHEZ-QUINTERO A1 Carlos Lopez戈麦首页斯A1卡塔琳娜州m . Quinzii年2018 UL //www.ez-admanager.com/content/90/15_Supplement/P3.329.abstract AB目的:阐明RMND1线粒体蛋白质翻译的功能和特征的影响RMND1突变体内生成和描述RMND1 -突变小鼠窝藏共同N239S RMND1突变。背景:RMND1属于sif2蛋白质家族分享DUF155未知函数的域。尽管RMND1函数是未知的,它内部的线粒体膜和线粒体参与翻译,可能在mitoribosome的组装和维护。RMND1突变患者(~ 30报道到目前为止)存在广泛的症状;先天性感音神经性耳聋,肌张力减退、发育迟缓和乳酸酸血症是最常见的临床表现与出生时的预期寿命2年。不太严重的表型与发病后4年,包括肾参与和温和的神经表型。病人肌肉和/或成纤维细胞显示严重缺陷的线粒体呼吸活动相结合,特别复杂的我和四世与损伤有关的线粒体蛋白质合成。目前,没有RMND1障碍存在的体内模型。设计/方法:我们评估寿命增长,从肌肉运动技能和线粒体功能,肾脏和大脑~ 1个月Rmnd1 k.i.老鼠。结果:纯合子RMND1敲入小鼠显示未能茁壮成长、肌肉无力、运动功能受损,而死在前两个月的生活。生化分析线粒体呼吸链酶(远端控制设备)在肌肉活动和肾脏显示复杂IV (COX)缺乏症。 In muscle, activity of citrate synthase (CS), an index of mitochondrial mass, was significantly increased, probably as a result of a compensatory mechanism.Conclusions: This murine model partially recapitulates clinical and biochemical features of the human disease. The generation and characterization of an in vivo model of RMND1 dysfunction is a critical first step towards an understanding of RMND1 function in mitochondrial translation and will be important to elucidate the pathomechanism of RMND1-dependent mitochondrial disease, and develop therapeutic approaches.Study Supported by: MDA295105 (Quinzii)Disclosure: Dr. SANCHEZ-QUINTERO has nothing to disclose. Dr. Lopez Gomez has nothing to disclose. Dr. Quinzii Hirano has nothing to disclose.

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