9.6.1 ABSTRACT: MOUSE GENETICS LABORATORY Director: David Largaespada, Ph.D. The Mouse Genetics Laboratory (MGL) shared resource provides cancer center members with access to stateof- the-art technologies required to create and efficiently study genetically modified mice. Genetically modified mice have been vital tools for cancer studies for many years, allowing one to determine the role of specific genes in cancer-relevant traits such as the immune responses, tumor initiation, and metastasis to name a few. Therefore, access to these technologies is critical to the ongoing work of the University of Minnesota Cancer Center. Cancer Center members have used this shared resource to create mouse models of myeloid leukemia, multiple myeloma, colorectal cancer and infant leukemia. Transgenic mice produced by this shared resource have been used to create a system for performing forward genetic screens for cancer genes in mice. Members have studied aspects of T and B cell development and immunity using transgehic mice created by this shared resource. These studies have relevance for understanding tumor surveillance and methods to break tolerance for anti-tumor immunity. We anticipate that this shared resource will continue to serve investigators that require in vivo genetic confirmation of important hypotheses touching many aspects of cancer biology. The MGL has served the Cancer Center for 10 years, indeed since the first Cancer Center Support Grant (CCSG) application. The MGL provides many interrelated services that require manipulation of mouse embryos or embryonic stem (ES) cells. We perform pronuclear microinjection for the creation of transgenic mice, blastocyst injection for projects that involve genetic manipulation of ES cells, in vitro fertilization, sperm/embryo cyropreservation, and any service that requires manipulation of early mouse embryos. We recently added another service, which is ES cell gene targeting and expansion. The MGL provides free ES cells, drugresistant mouse embryo fibroblasts (MEFs), and plasmid vectors. Finally, we provide free consultation on mouse husbandry and strain maintenance, the design of ES cell gene targeting experiments, and the use of mouse models for cancer-related research in general. The MGL shared resource leader is Dr. David Largaespada, an Associate Professor in the Department of Genetics, Cell Biology and Development. He has been this shared resource's leader or co-leader since the beginning of the MGL and sets priorities for scientific use of the MGL in consultation with Cancer Center member users and the Rodent Advisory Committee (RAC) of the University of Minnesota. The MGL currently consists of three full time staff members in addition to Dr. Largaespada.

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