中國(guó)科學(xué)院廣州生物醫(yī)藥與健康研究院研究員賴(lài)良學(xué)與美國(guó)愛(ài)默瑞大學(xué)教授李曉江合作,，在南方醫(yī)科大學(xué)教授顧為望協(xié)助下，采用轉(zhuǎn)基因克隆技術(shù)成功獲得了人類(lèi)亨廷頓舞蹈癥的轉(zhuǎn)基因豬模型,。轉(zhuǎn)基因豬模型表現(xiàn)出亨廷頓舞蹈癥的典型癥狀,。研究成果于8月8日在國(guó)際權(quán)威雜志Human Molecular Genetics上發(fā)表。
賴(lài)良學(xué)領(lǐng)導(dǎo)的研究團(tuán)隊(duì)通過(guò)運(yùn)用體細(xì)胞轉(zhuǎn)基因技術(shù)與體細(xì)胞核移植技術(shù),，與李曉江研究團(tuán)隊(duì)構(gòu)建亨廷頓蛋白轉(zhuǎn)基因載體密切合作,，成功獲得6頭亨廷頓舞蹈癥轉(zhuǎn)基因豬；同時(shí)首次在轉(zhuǎn)基因豬大腦中發(fā)現(xiàn)與人類(lèi)亨廷頓舞蹈癥患者腦中類(lèi)似的神經(jīng)細(xì)胞凋亡現(xiàn)象,，這在亨廷頓舞蹈癥的動(dòng)物模型中還是第一次見(jiàn)到,。
該研究成果對(duì)于亨廷頓舞蹈癥病理發(fā)生機(jī)制的研究以及治療藥物開(kāi)發(fā)具有重要的意義，同時(shí),，該成果也使人們更加認(rèn)識(shí)到建立人類(lèi)遺傳性疾病的轉(zhuǎn)基因大動(dòng)物模型的重要性,。
亨廷頓舞蹈癥（Huntington chorea)，又名慢性進(jìn)行性舞蹈病,，是一種緩慢起病的遺傳性神經(jīng)退化疾病,，在人群中發(fā)病率為萬(wàn)分之一左右。目前國(guó)內(nèi)外醫(yī)學(xué)界把“舞蹈病”列為不治之癥,。此前,，用于亨廷頓舞蹈癥研究的動(dòng)物模型主要是嚙齒類(lèi)（大鼠、小鼠）,。由于在生理,、代謝等各個(gè)方面與人類(lèi)差別巨大，嚙齒類(lèi)模型還存在一些與人類(lèi)疾病癥狀不一致的表現(xiàn),，這對(duì)于病理的研究,、特別是一些治療藥物和手段的研究非常不利。此前,，國(guó)際上其他科學(xué)家試圖建立亨廷頓舞蹈病的大動(dòng)物模型,，但均未獲得成功。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
