CORE--GENE TARGETING AND TRANSGENICS

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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.