中国科学院广州生物医药与健康研究院研究员赖良学与美国爱默瑞大学教授李晓江合作，在南方医科大学教授顾为望协助下，采用转基因克隆技术成功获得了人类亨廷顿舞蹈症的转基因猪模型。转基因猪模型表现出亨廷顿舞蹈症的典型症状。研究成果于8月8日在国际权威杂志Human Molecular Genetics上发表。
赖良学领导的研究团队通过运用体细胞转基因技术与体细胞核移植技术，与李晓江研究团队构建亨廷顿蛋白转基因载体密切合作，成功获得6头亨廷顿舞蹈症转基因猪；同时首次在转基因猪大脑中发现与人类亨廷顿舞蹈症患者脑中类似的神经细胞凋亡现象，这在亨廷顿舞蹈症的动物模型中还是第一次见到。
该研究成果对于亨廷顿舞蹈症病理发生机制的研究以及治疗药物开发具有重要的意义，同时，该成果也使人们更加认识到建立人类遗传性疾病的转基因大动物模型的重要性。
亨廷顿舞蹈症（Huntington chorea)，又名慢性进行性舞蹈病，是一种缓慢起病的遗传性神经退化疾病，在人群中发病率为万分之一左右。目前国内外医学界把“舞蹈病”列为不治之症。此前，用于亨廷顿舞蹈症研究的动物模型主要是啮齿类（大鼠、小鼠）。由于在生理、代谢等各个方面与人类差别巨大，啮齿类模型还存在一些与人类疾病症状不一致的表现，这对于病理的研究、特别是一些治疗药物和手段的研究非常不利。此前，国际上其他科学家试图建立亨廷顿舞蹈病的大动物模型，但均未获得成功。
推荐原文出处：
Human Molecular Genetics doi:10.1093/hmg/ddq313
Expression of Huntington's disease protein results in apoptotic neurons in the brains of cloned transgenic pigs
Dongshan Yang1, Chuan-En Wang2, Bentian Zhao1, Wei Li1, Zhen Ouyang1, Zhaoming Liu1, Huaqiang Yang1, Pei Fan3, Ashley O'Neill2, Weiwang Gu3, Hong Yi4, Shihua Li2, Liangxue Lai1,* and Xiao-Jiang Li2,*
1 Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China, 2 Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA, 3 Institute of Comparative Medicine and Center of Experimental Animals, Southern Medical University, Guangzhou 510515, China and 4 The Robert P. Apkarian Integrated Electron Microscopy Core, Emory University, Suite E106, Cherry L. Emerson Hall 1521 Dickey Drive, Atlanta, GA 30322, USA
Neurodegeneration is a hallmark of many neurological diseases, including Alzheimer's, Parkinson's and the polyglutamine diseases, which are all caused by misfolded proteins that accumulate in neuronal cells of the brain. Although apoptosis is believed to contribute to neurodegeneration in these cases, genetic mouse models of these diseases often fail to replicate apoptosis and overt neurodegeneration in the brain. Using nuclear transfer, we generated transgenic Huntington's disease (HD) pigs that express N-terminal (208 amino acids) mutant huntingtin with an expanded polyglutamine tract (105Q). Postnatal death, dyskinesia and chorea-like movement were observed in some transgenic pigs that express mutant huntingtin. Importantly, the transgenic HD pigs, unlike mice expressing the same transgene, displayed typical apoptotic neurons with DNA fragmentation in their brains. Also, expression of mutant huntingtin resulted in more neurons with activated caspase-3 in transgenic pig brains than that in transgenic mouse brains. Our findings suggest that species differences determine neuropathology and underscore the importance of large mammalian animals for modeling neurological disorders.
