转基因动物在生物制药工业中的应用

简要论述了转基因动物的概念、制作方法及应用领域,回顾了转基因动物技术的发展及现状,分析了转基因动物与克隆动物的区别.就转基因动物在制药工业和生物医药领域中的国内外研究与开发应用情况进行了阐述,同时展望了转基因动物制药的发展前景及对社会的影响.     

转基因动物食品安全性评价研究

鉴于转基因动物食品安全性尚未有定论,为加强转基因动物食品安全管理,本文提出了转基因动物食品安全性评价的四原则和五项主要内容,"四原则"是科学原则、实质等同性原则、个案原则、逐步原则;"五项主要内容"是转基因动物本身的特性,转基因动物食品有无毒性和过敏性,转基因动物食品有无激素含量和标记基因,转基因动物食品的售后状况以及其他相关因素,指出了建立一套与国际接轨的适合我国国情的转基因动物食品安全性评价方法是目前我国食品安全领域需要解决的问题.     

转基因动物生物安全研究与评价

随着转基因动物在新品种培育、异种器官移植、生物反应器和疾病模型等方面的研究与发展,转基因动物的生物安全性引起了人们的广泛关注。目前,各国政府与机构已制定了相应的法律法规来规范转基因动物的研究与应用。文中介绍了转基因动物生物安全研究的内容、评价原则、评价政策与程序、上市或有望上市的转基因动物产品。最后,对转基因动物及其产品的研究与应用进行了展望。     

转基因动物生物安全性分析

<正>随着转基因技术在医药、农业、环保、生物材料等方面的应用,转基因动物在各个领域内产生了重大的变革。然而任何技术的出现都是一把双刃剑,转基因动物在一定层面上也备受争议,因此,转基因动物生物安全性评估显得尤为重要。从转基因动物自身安全、食品安全和环境安全3个方面进行了分析,并概述了国内外转基因动物生物安全管理现状。     

转基因动物育种产业化现状和发展趋势

与传统的育种方法相比,转基因动物育种具有诸多优点,利用该技术得到的转基因鼠、转基因羊、转基因牛等动物,已经显示出巨大的商业前景。本文从动物转基因技术入手,结合相关专利,分析了近几年转基因动物育种技术的发展和趋势。重点从转基因动物育种在医药和农业上的应用,分析国内外目前的产业化状况。最后根据产业化中的一些问题及国内外差异,对我国转基因动物育种产业化提出建议,并进行了展望。     

转基因动物研究及其应用

本文综述了转基因动物的研究过程、制作方法、转基因动物的应用及其取得的成就,并展望了转基因动物产品的应用前景。     

转基因动物及其产品的安全评估方法研究进展

目前,转基因动物技术发展迅速并广泛应用于食品、医药、农业和生物材料等众多领域,带来了巨大的经济效益和社会效益,且发展潜力巨大。同时,转基因动物及其产品的安全性问题也日益突出,表现在转基因动物本身及产品安全性和环境安全性两个主要方面。"实质等同性原则"是国际上转基因动物安全性评价的基本原则。从转基因动物及其产品作为食品、药品等的安全性评估;从转基因动物对生态环境安全和影响的评估和非预期效应的评估等三个方面进行了阐述,并对我国转基因动物评价体系的构建提出建议。     

转基因动物研究新进展

我们曾对转基因动物的制作方法、转基因动物研究的应用、转基因的表达特征及提高转基因表达的策略等作过专题综述＾「１」。而这之后在转基因动物的研究方面又获得了许多新进展,其中转线粒体动物的问世拓宽了转基因动物的研究内容。在制作转基因动物的方法上,１９９８－１９９９年世界上先后报道了三种新方法：即由Ｓｃｈｎｉｅｋ等报道的体细胞核移植技术实现转基因,由Ａｎｔｈｏｎｙ Ｗ．Ｓ．Ｃ等报道的通过用逆转录病毒载体感     

转基因动物器官移植的安全问题及对策研究

从转基因动物器官移植的概念入手,就转基因动物器官移植的安全问题作了分析,指出了目前转基因动物器官移植遇到的最大障碍是跨物种感染,并就加强转基因动物器官移植安全管理提出了一些对策.     

提高转基因表达水平的策略

随着转基因相关技术的发展,转基因动物技术在许多方面得到了成功应用.但外源基因在体内的表达仍然难以预测,特别是大动物的转基因,由于制备效率低下,因而难以筛选出足够的高表达的阳性动物数.基因表达调控研究对提高外源基因在动物体内的表达水平提供了一些新手段,本就避免转基因的位置效应、控制外源基因在动物宿主基因组中的整合、提高转基因的表达效率、构建转基因载体和使用外源基因需要注意的问题等进行综述.     

草坪草育种研究进展 (综述)

介绍草坪草传统育种和转基因育种的历史与现状,概述草坪转基因育种的操作过程,对植物特别是草坪草转基因过程中存在的一些问题如基因丢失,基因沉默,基因流引起的转基因安全性等进行评述。     

中国转基因作物风险评估技术研究进展

现代生物技术的发展为利用外源基因培育优良作物品种提供了新的途径,目前国内外已培育出多个高抗害虫的转基因作物。但是,人们对转基因作物潜在的风险尚存在疑问,这是目前转基因作物是否能进一步获准商品化生产的一个重要原因。综述了中国转基因作物研究和转基因产品安全性检测技术取得的主要进展,对我国转基因作物的研究前景进行了展望,并对将来的工作提出了几点建议。     

转基因植物检测技术的研究进展

现代植物基因工程使转基因植物及其产品越来越多地进入人们的生活,转基因植物安全性在世界范围内引起了广泛关注,对转基因植物检测技术的需求也越来越紧迫。就转基因植物检测技术的研究进展进行综述,重点介绍以基因和蛋白为目标的检测技术,包括PCR、ELISA和基因芯片技术的最新进展,并对不同方法的优缺点进行对比。此外,提出对特定代谢产物的检测是转基因植物检测的重要组成部分,是以后检测技术的发展趋势之一。最后,以差异蛋白为检测目标,结合研究工作提出基于双向电泳技术的转基因植物检测方法及其产品溯源方案。     

转基因作物对土壤微生物的影响

全球范围内转基因农作物的大量种植不仅带来巨大的经济利益,同时也引发了人们关于转基因作物对包含土壤微生物在内的土壤生态系统的潜在风险的忧虑.转基因作物对土壤微生物的影响包括外源基因表达蛋白对非靶标土壤微生物的直接影响,也包括因外源基因导入而植物根系分泌物组分变化引起的间接影响.目前,对转基因作物的大多数研究表明,转基因作物能引起土壤微生物种群数量和结构的变化.但是,转基因作物对土壤微生物的影响力度有大有小,持续时间有长有短,评价不一.本文综述了不同种类转基因作物对土壤微生物的影响,对转基因作物种类、试验技术和原则等影响评价结果准确性的因素进行了讨论,提出了进一步研究需要注意的问题.     

The effects of aromatase overexpression on mammary growth and gene expression in the aromatase x transforming growth factor alpha double transgenic mice

The transforming growth factor alpha (TGF) and its receptor (EGFR) are expressed in many breast cancers. Typically, the progression of estrogen dependent primary breast cancers into a hormone-independent state, due to the loss of the estrogen receptor, is associated with increased levels of TGF and EGFR, leading to aggressive breast carcinomas. The relationship between breast tumorigenesis and TGF is evident in the transgenic mice overexpressing TGF in the mammary glands. In the aromatase transgenic mice, the mammary glands exhibit preneoplastic developments but do not form frank tumors. To test the interactions between growth factor overexpression with tissue estrogen, we have crossed the aromatase transgenic mice with the TGF transgenic mice to produce a double transgenic strain. The histological data for the mammary glands of aromatase x TGF double transgenic mice show that these mice develop hyperplastic changes similar to the aromatase parental strain but no tumors are formed. Consistently, the expression of cyclin D1 and PCNA is diminished in the double transgenic strain as compared to the parental strains. In addition, the expression of TGF, EGF and EGFR are also decreased in the double transgenic strain, suggesting that continuous estrogen presence in the tissue due to aromatase overexpression downregulates the expression of EGFR and its ligands.     

A peripheral mechanism preserves self-tolerance to a secreted protein in transgenic mice

We have examined mechanisms of tolerance to circulating self-proteins in mice that are transgenic for human insulin. Normal, nontransgenic mice develop serum antibody responses when injected with human insulin in CFA; syngeneic transgenic mice do not. B cell responsiveness was assessed by immunizing with human insulin coupled to a T-independent Ag, Brucella abortus. No differences were found in the numbers of insulin-specific splenic plaque-forming cells between transgenic and nontransgenic mice suggesting that insulin-specific B cells are not tolerant in transgenic mice. Similarly, APC from transgenic and nontransgenic mice display no differences in their ability to process and present human insulin to human insulin-specific T cells in vitro. However, marked differences were detected between transgenic and nontransgenic T cells. Lymph node T cells from transgenic mice primed with human insulin provided no detectable helper activity for secondary antibody responses to human insulin whereas, lymph node T cells from nontransgenic mice did. Nevertheless, lymph node T cells from transgenic mice developed significant proliferative responses to human insulin. Lymph node T cells obtained from transgenic and nontransgenic mice were fused to BW5147 and human insulin-specific T cell hybridomas were generated. The fact that human insulin-specific T cell hybridomas were obtained from the transgenic mice suggests that these T cells were not clonally deleted. In addition, APC from transgenic mice did not stimulate human insulin-specific hybridomas from normal mice in the absence of exogenous insulin. We suggest that T cells specific for human insulin are not deleted in the thymus of transgenic mice because APC in the thymus do not bear the requisite levels of endogenous human insulin/Ia complexes. Therefore, we conclude that tolerance in the transgenic mice is preserved by peripheral mechanisms.     

逆转录病毒与转基因鸡

摘要：随着生物制药业的迅速发展,转基因鸡输卵管生物反应器正逐渐成为人们关注的焦点,转基因鸡以其卓越的优势必将成为科学研究的热点和生物制药领域的新兴产业之一。目前,转基因鸡最成功的制备方法即逆转录病毒介导法,并已成功制备出表达标记基因的转基因鸡。本文主要综述了逆转录病毒载体制备转基因鸡的优势,逆转录病毒制备转基因鸡的方法和转基因鸡的研究进展,同时也讨论了转基因鸡的意义和存在问题。     

Alloreactive lymphocytes from T cell receptor (beta-chain) transgenic mice do not mediate a graft-versus-host reaction.

The injection of mature T cells into a tolerant or immunocompromised allogeneic host animal produces a graft versus host response (GVHR) that can result in splenomegaly, immunosuppression and death of the host animal. We demonstrate here that lymphocytes from T cell receptor beta-chain (TCR-beta) transgenic mice, in which the expression of the transgene inhibits endogenous beta- and gamma-gene rearrangements and thus causes abnormal T cell development, are unable to mediate a GVHR. The GVHR was measured after the injection of lymphocytes from transgenic mice into normal F1 mice and also after transplantation of bone marrow and lymphocytes from transgenic mice into lethally irradiated F1 recipients. In both systems, cells from transgenic mice failed to produce a significant GVHR. Cells from the transgenic mice were able to recognize the foreign histocompatibility Ag of the host in vitro and in vivo although the transgenic mice rejected skin grafts more slowly than controls. Thus, lymphocytes from transgenic mice were unable to produce a GVHR despite the presence of alloreactive T cells. These results suggest that lymphocytes from TCR-beta transgenic mice fail to mediate a GVHR either because lymphocytes with a single transgenic TCR-beta chain have a limited ability to recognize allogeneic cells in vivo or because the transgenic mice lack lymphocyte subsets that are important for the mediation of a GVHR.     

Simple Databases to Monitor the Generation and Organisation of Transgenic Mouse Colonies

The generation and analysis of transgenic mice has become an important tool to progress our understanding of human and mouse gene function and its association with human genetic diseases. Animal models, based on genetically modified mice, both standard transgenic and knock-out animals, are increasingly being used world-wide. Monitoring of transgenic mouse production and transgenic mouse colonies is required to efficiently manage the resources that are available. Here, I describe three independent FileMaker databases (transgenics, mymouse and cages) that have been developed to track the generation of transgenic mice, the organisation of transgenic mouse colonies and the distribution of mice in cages. These three databases are freely available for academic use.