PDF(Pubmed)
Abstract：
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal childhood motoneuron disease caused by mutations in the IGHMBP2 gene. It is characterized by muscle weakness, initially affecting the distal extremities due to the degeneration of spinal α-motoneurons, and respiratory distress, due to the paralysis of the diaphragm. Infantile forms with a severe course of the disease can be distinguished from juvenile forms with a milder course. Mutations in the IGHMBP2 gene have also been found in patients with peripheral neuropathy Charcot-Marie-Tooth type 2S (CMT2S). IGHMBP2 is an ATP-dependent 5\'→3\' RNA helicase thought to be involved in translational mechanisms. In recent years, several animal models representing both SMARD1 forms and CMT2S have been generated to initially study disease mechanisms. Later, the models showed very well that both stem cell therapies and the delivery of the human IGHMBP2 cDNA by AAV9 approaches (AAV9-IGHMBP2) can lead to significant improvements in disease symptoms. Therefore, the SMARD1 animal models, in addition to the cellular models, provide an inexhaustible source for obtaining knowledge of disease mechanisms, disease progression at the cellular level, and deeper insights into the development of therapies against SMARD1.
摘要：
脊髓性肌萎缩伴呼吸窘迫1型(SMARD1)是一种由IGHMBP2基因突变引起的致命性儿童运动神经元疾病。它的特点是肌肉无力，最初由于脊髓α运动神经元的退化而影响四肢远端，呼吸窘迫,由于隔膜的瘫痪。具有严重病程的婴儿形式可以与具有较温和病程的青少年形式区分开。在患有Charcot-Marie-Tooth2S型周围神经病变（CMT2S）的患者中也发现了IGHMBP2基因的突变。IGHMBP2是一种ATP依赖性5'→3'RNA解旋酶，被认为参与翻译机制。近年来,已经建立了几种代表SMARD1形式和CMT2S的动物模型，以初步研究疾病机制。稍后，这些模型很好地表明,干细胞疗法和通过AAV9方法递送人IGHMBP2cDNA(AAV9-IGHMBP2)可以导致疾病症状的显著改善.因此,SMARD1动物模型，除了细胞模型，为获得疾病机制知识提供取之不尽的来源，细胞水平的疾病进展，以及对SMARD1疗法发展的更深入的见解。
