Description: (Applicants Description) Advances in experimental manipulation of the laboratory mouse via gene expression, mutation, or deletion strategies have propelled major progress in the fields of cell, developmental and tumor biology. Transgenic and targeted mice serve as in vivo models of gene function (or dysfunction) and thereby contribute greatly to our understanding of dynamic, complex oncogenic mechanisms. These models are also invaluable in studies of the prevention and treatment, as well as the etiology of cancer and other diseases. For many research programs, the disadvantages or deterrents to the use of these mouse models are the substantial cost, time, equipment, and expertise required for their derivation and examination. Therefore, as a shared resource, the primary purpose of the Mouse Models Core Facility is to provide proficient, affordable generation of genetically modified mice for both basic and translational cancer research by Moffitt investigators. The specific objectives are to: Advise investigators on overall strategy and the design of transgenic and targeting vectors; provide embryonic stem (ES) cells and instruction in their culture, transfection, selection, and screening; provide pronuclear DNA microinjection services to generate transgenic founder mice; provide blastocyst microinjection and morula aggregation services to generate germline chimeras from gene-targeted ES cells; advise and assist investigators in the genotypic and phenotypic analysis of mice. From a total operating cost of $147,360, we are requesting $46,096 from the CCSG allocation, an amount that represents approximately 31 percent of the total operating budget. These funds will support a portion of the facility staff salaries and instrument service.