最近，科学家成功的将导致腓骨肌萎缩症的变异基因导入果蝇体内。腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)亦称遗传性运动感觉神经病(hereditary motor and sensoryneuropathy,HMSN),是神经系统最常见的遗传性周围神经疾病。全球每2500人就有一人患有此病。患者临床主要特征是四肢远端进行性的肌无力和萎缩伴感觉障碍，重者导致感觉丧失和四肢畸形，目前并没有有效治疗和预防方法。科学家通过将致病基因导入果蝇，建立腓骨肌萎缩症的模式生物，有助于查明腓骨肌萎缩症患病分子机制和寻找治疗方法。

先前的研究发现，腓骨肌萎缩症患者多伴有YARS基因变异。YARS基因是体内合成蛋白质的一种重要酶的编码基因。最新的研究首次将YARS基因与腓骨肌萎缩症联系在一起。

研究人员设计将四种不同的YARS变异基因导入果蝇，导入正常YARS基因的果蝇没有出现任何疾病症状，携带变异YARS基因的果蝇均表现出腓骨肌萎缩症症状，如运动能力下降，神经末梢变性。

推荐原始出处：

PNAS June 26, 2009, doi: 10.1073/pnas.0905339106

Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot–Marie–Tooth neuropathy

Erik Storkebauma,b,1, Ricardo Leit?o-Gon?alvesa,b,c,d,1, Tanja Godenschwegee, Leslie Nanglef,g, Monica Mejiae, Inge Bosmansa,b, Tinne Oomsc,d, An Jacobsc,d, Patrick Van Dijckh,i, Xiang-Lei Yangf, Paul Schimmelf,2, Koen Norgaa,j, Vincent Timmermanc,d, Patrick Callaertsa,b,1,3 and Albena Jordanova

Dominant-intermediate Charcot–Marie–Tooth neuropathy (DI-CMT) is characterized by axonal degeneration and demyelination of peripheral motor and sensory neurons. Three dominant mutations in the YARS gene, encoding tyrosyl-tRNA synthetase (TyrRS), have so far been associated with DI-CMT type C. The molecular mechanisms through which mutations in YARS lead to peripheral neuropathy are currently unknown, and animal models for DI-CMTC are not yet available. Here, we report the generation of a Drosophila model of DI-CMTC: expression of the 3 mutant—but not wild type—TyrRS in Drosophila recapitulates several hallmarks of the human disease, including a progressive deficit in motor performance, electrophysiological evidence of neuronal dysfunction and morphological signs of axonal degeneration. Not only ubiquitous, but also neuron-specific expression of mutant TyrRS, induces these phenotypes, indicating that the mutant enzyme has cell-autonomous effects in neurons. Furthermore, biochemical and genetic complementation experiments revealed that loss of enzymatic activity is not a common feature of DI-CMTC-associated mutations. Thus, the DI-CMTC phenotype is not due to haploinsufficiency of aminoacylation activity, but most likely to a gain-of-function alteration of the mutant TyrRS or interference with an unknown function of the WT protein. Our results also suggest that the molecular pathways leading to mutant TyrRS-associated neurodegeneration are conserved from flies to humans.