NIH上马“敲除老鼠计划”
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发布日期: 2006-09-12 12:07 文章来源: 丁香园 - 医药生命科学动态跟踪
关键词: 基因敲除 Knockout NIH 基因突变 点击次数:

    美国国家健康研究所已经启动了“敲除老鼠计划”(KOMP),这是一项工作量巨大的研究,期望能够敲除掉老鼠基因组中超过三分之一的基因。今天,研究所指定了四个研究中心,它们获得了为期5年总额共计5000万美元的资助来创建突变细胞系和老鼠,期望能够提供给研究者针对任何疾病的突变小鼠或任何他们想要研究的发育相关基因。 

    其中三个中心,加利福尼亚州儿童医院Oakland研究所,加州大学戴维斯分校Veterinary医学院,英国Hinxton 的Wellcome Trust Sanger研究所共同工作创建大约5000只不同的敲除小鼠。第四个中心位于纽约Tarrytown Regeneron Pharmaceuticals公司,它们打算创建出大约3500只另外的突变小鼠用于药物研发项目。“NIH已经选择一些非常棒的研究人员,”耶鲁大学的一位老鼠研究者这样说道。

    NIH这项研究计划是敲除老鼠基因组中每一个基因全球努力的一部分(Science,30 June,p 1862)。今年一月,欧洲和加拿大分别开展了欧洲限制性老鼠突变计划(EUCOMM)和北美限制性老鼠突变计划,这些计划的共同目标是创建出超过30,000个基因敲除的胚胎干细胞。中国打算开展一项类似的研究计划敲除人类和老鼠共有的25,000个基因,目前已经完成了11,000个不同敲除。通过协调他们的努力,这些计划有希望缩短差距。

    Sanger研究所也是EUCOMM计划的领导成员,但是所长Allan Bradley说这两项研究计划并无重叠之处,“KOMP和EUCOMM的研究者将肩并肩的工作,但是他们将分别瞄准不同系列的基因。”

    通过一个设立在Jackson实验室的数据库,科研界可追踪KOMP的研究进展,这个实验室位于在缅因州Bar Harbor。该数据库将得到250万美元的资助来搜集,分析和传播与这项计划相关的信息。另外250万美元将拨发给费城的宾夕法尼亚大学和多伦多的Mount Sinai医院用以改善KOMP中心使用的试剂的特性。

    在未来的6-9个月,研究者们便会开始收割KOMP的成果,该项计划的主管Colin Fletcher说道,那时他们将可以从Regeneron公司和加州大学戴维斯分校订购用于他们自己敲除小鼠的材料。明年秋天,NIH将建立一个或更多的分中心以便研究者能尽快得到他们所需的敲除小鼠。

    “这将节省研究者大量的金钱和时间,极大的加速老鼠研究的步伐”,宾夕法尼亚大学癌症中心的老鼠研究者M  Celeste Simon说道,“这是NIH一项非常明智的投资。”

    http://sciencenow.sciencemag.org/cgi/content/full/2006/907/1

    NIH Launches Attack on Mouse Genome

    The National Institutes of Health (NIH) has kicked off its Knockout Mouse Project (KOMP), a massive effort to delete over a third of the genes in the mouse genome. Today, the institute named four centers that together will receive nearly $50 million over 5 years to create mutant cell lines and mice. The resource is expected to provide researchers with a mouse mutant for whatever disease or development gene they want to study.

    Three of the centers--Children's Hospital Oakland Research Institute in California, the School of Veterinary Medicine at the University of California (UC), Davis, and the Wellcome Trust Sanger Institute in Hinxton, U.K.--will work together to make about 5000 unique knockouts. The fourth center, Regeneron Pharmaceuticals in Tarrytown, New York, plans to generate about 3500 additional mutants using technology it has developed for its drug-discovery program. "NIH has picked some great people," says Marina Picciotto, a mouse researcher at Yale University.

    The NIH program is part of a global endeavor to knock out every gene in the mouse genome (Science, 30 June, p. 1862). In January, Europe and Canada embarked on the European Conditional Mouse Mutagenesis Program (EUCOMM) and the North American Conditional Mouse Mutagenesis Project, respectively, which have a combined goal of creating more than 30,000 knockouts in embryonic stem cells. China has plans for a similar resource. Mice and humans share similarity in some 25,000 genes, yet to date only about 11,000 different knockouts have been made. By coordinating their efforts, the projects hope to close this gap.

    The Sanger Institute is also one of the leaders of the EUCOMM effort, but Sanger Director Allan Bradley says there will be no overlap between the two programs. "KOMP and EUCOMM researchers will be working side by side, but they'll each be targeting a different set of genes," he says.

    The research community will be able to track KOMP's progress via a database set up at the Jackson Laboratory in Bar Harbor, Maine, which will receive $2.5 million to collect, analyze, and disseminate information relevant to the project. Another $2.5 million will go to the University of Pennsylvania in Philadelphia and the Mount Sinai Hospital in Toronto to improve the performance of the reagents used by the KOMP centers.

    Researchers should begin reaping KOMP's benefits in 6 to 9 months, says program director Colin Fletcher, when they can start ordering materials from Regeneron and UC Davis to make their own knockout mice. By next fall, he says, NIH will have set up one or more distribution centers that will quickly get knockouts into the hands of researchers who need them.

    "That's going to save investigators lots of money and time and greatly accelerate the pace of mouse research," says M. Celeste Simon, a mouse researcher at the University of Pennsylvania Cancer Center. "It's a very wise investment for NIH."


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