CORE--GENE TARGETING AND TRANSGENICS

在过去的十年里，转基因小鼠越来越多地成为许多新的生物来源。 癌症模型有助于阐明肿瘤发展和进展的途径。随着人类和小鼠基因组序列的完成以及对这些基因组进行功能注释的大规模努力的开始，这一趋势将继续加速。转基因小鼠的生产需要高度专业化的仪器和专业知识，这在大多数实验室都不具备。基因靶向和转基因资源的使命是确保RPCI的研究人员能够获得最先进的转基因小鼠技术、方法和动物模型。资源联合主任从项目的最早规划阶段（即设计载体时）开始向调查人员提供指导， 在表型分析期间进入项目的高级阶段。资源技术人员执行专门的ES细胞和胚胎操作方法来产生转基因小鼠。该资源有几个核心载体，已成功用于制备修饰小鼠，并根据需要免费分发给用户。新的资源服务包括使用BAC DNA制备转基因小鼠，以及使用cre LoxP方法维护cre转基因小鼠进行二级基因组操作。在过去的三年中，该资源为三个CCSG计划提供了超过94个新的转基因品系（11个敲除和83个转基因品系，来自23个构建体）。它还协助开发了独特的小鼠模型，有助于理解印记及其在癌症中的作用，几个重要基因的调节，以及两种模拟染色体重排的转基因模型 与特定的人类癌症有关。由于正在进行的招募和需要开发转基因小鼠模型的项目，预计该设施的使用量将继续增加。

During the past decade, genetically modified mice have increasingly been a source of many new cancer models that have helped elucidate pathways contributing to tumor development and progression. With the completion of the human and mouse genome sequences and the initiation of large-scale efforts to functionally annotate these genomes, this trend will continue to accelerate. Production of genetically modified mice requires highly specialized instrumentation and expertise not available in most labs. The mission of the Gene Targeting and Transgenics Resource is to ensure that investigators at RPCI have access to state-of-the-art transgenic mouse technologies, methods, and animal models. Resource Co-Directors provide guidance to investigators from the earliest planning stages of the project when vectors are designed, to advanced stages of the project during phenotype analysis. Resource technicians perform the specialized ES cell and embryo manipulation methods to generate the genetically modified mice. The Resource has several core vectors that have been successfully used in the preparation of modified mice, and these are freely distributed to users as needed. New Resource services include preparation of transgenic mice using BAC DNA, and maintenance of cre transgenic mice for secondary genomic manipulations using cre LoxP methods. During the past three years, the Resource has provided over 94 new genetically modified lines (11 knockouts and 83 transgenics from 23 constructs) for three CCSG Programs. It also has assisted in the development of unique mouse models that contribute to understanding imprinting and its role in cancer, regulation of several important genes, and two transgenic models which mimic chromosome rearrangements associated with specific human cancers. Projected use of the facility is expected to continue to rise due to ongoing recruitment and projects requiring the development of transgenic mouse models.