application): The main purpose of the Transgenic Core is to make available a service facility that will ensure the capacity of each DERC member to produce (a) transgenic mice and chimeric mice derived from transfected embryonal stem cells and (b) transgenic rats. Not only will this Core facility make available specialized technology to a wide group of people, it will also result in a great economy of expense and effort by obviating the duplication of a highly technical skill which requires expensive, specialized equipment and animal facilities. The availability of genetically modified, inbred, strains of mice and rats is central to our ability to understand physiologic and immunologic aspects of diabetes. This Core, therefore, represents a hub of the center, which reaches out to all of the activities in this proposal, and a major portion of the diabetes community at Yale. The Yale Comprehensive Cancer Center has an existing Core facility for the provision of transgenic mice and for embryo freezing. Investigators conducting cancer-related research receive a discount for these services. The Cancer Center generated transgenic mice are produced on a (B6xSJL)F2 strain of mouse. There is at present no provision of inbred mice, transgenic rats or chimeric rodents. That Core facility therefore is not optimal for the critical features for which the DERC Core is required, namely the generation of transgenic animals on diabetes prone or diabetes resistant strains, in rats, or the application of the ES cell technology using chimeric and eventually germ line transmission mice for the study of diabetes. There are no plans to make all of these services available from the Cancer Center Core, although facilities to make chimeric mice are planned for the coming year. It is likely that substantial training time will be required to establish this Cancer Center Core, but realistically that should be up and running within approximately one year. We view it as a positive to have a second Core facility at Yale since, in our experience, the demand for generation of chimeric rodents has greatly exceeded our own capacity for producing these animals. This will allow the DERC Animal Genetics and Breeding Core to take on the breeding of additional animals for diabetes research. There is a commercial facility (DNAX) which supplies transgenic mice. This, however, at present only offers mice on a non-inbred genetic background which is much less useful to the members of this DERC. Moreover, there are no plans to make inbred transgenics available commercially on the NOD background. It should be understood that an alternative is to generate transgenic mice on a non-inbred background followed by back-crossing of these animals onto a given inbred background, such as NOD. In order for this to be genetically homogeneous, however, requires greater than 10 back-crosses, which involves enormous expense and time and which puts DERC members at a significant disadvantage as compared with investigators who can utilize in-bred mice.
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