Jackson G R, Salecker I, Dong X, Yao X, Arnheim N, Faber P W, MacDonald M E, Zipursky S L
Department of Neurology, University of California, Los Angeles School of Medicine, 90095, USA.
Neuron. 1998 Sep;21(3):633-42. doi: 10.1016/s0896-6273(00)80573-5.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Disease alleles contain a trinucleotide repeat expansion of variable length, which encodes polyglutamine tracts near the amino terminus of the HD protein, huntingtin. Polyglutamine-expanded huntingtin, but not normal huntingtin, forms nuclear inclusions. We describe a Drosophila model for HD. Amino-terminal fragments of human huntingtin containing tracts of 2, 75, and 120 glutamine residues were expressed in photoreceptor neurons in the compound eye. As in human neurons, polyglutamine-expanded huntingtin induced neuronal degeneration. The age of onset and severity of neuronal degeneration correlated with repeat length, and nuclear localization of huntingtin presaged neuronal degeneration. In contrast to other cell death paradigms in Drosophila, coexpression of the viral antiapoptotic protein, P35, did not rescue the cell death phenotype induced by polyglutamine-expanded huntingtin.
亨廷顿舞蹈症（HD）是一种常染色体显性神经退行性疾病。致病等位基因包含可变长度的三核苷酸重复序列扩增，该序列在亨廷顿舞蹈症蛋白（亨廷素）的氨基末端附近编码多聚谷氨酰胺序列。多聚谷氨酰胺扩增的亨廷素而非正常亨廷素会形成核内包涵体。我们描述了一种亨廷顿舞蹈症的果蝇模型。在复眼中的感光神经元中表达了含有2个、75个和120个谷氨酰胺残基序列的人类亨廷素氨基末端片段。与人类神经元一样，多聚谷氨酰胺扩增的亨廷素会诱导神经元变性。神经元变性的发病年龄和严重程度与重复序列长度相关，并且亨廷素的核定位预示着神经元变性。与果蝇中的其他细胞死亡模式不同，病毒抗凋亡蛋白P35的共表达并不能挽救由多聚谷氨酰胺扩增的亨廷素诱导的细胞死亡表型。
