PT -期刊文章盟玛丽亚j . SANCHEZ-QUINTERO AU -卡洛斯·洛佩兹·戈麦斯盟卡塔琳娜州m . Quinzii TI -小说RMND1敲入小鼠概括(P3.329)患者进行临床和生化异常观察DP - 2018年4月10 TA -神经病学PG - P3.329 VI - 90 IP - 15补充4099 - //www.ez-admanager.com/content/90/15_Supplement/P3.329.short 4100 - http://n.首页neurology.org/content/90/15_Supplement/P3.329.full所以Neurology2018 4月10;90 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。 Biochemical analysis of mitochondrial respiratory chain enzymes (RCE) activities in muscle and kidney showed complex IV (COX) deficiency. 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.