application): The introduction of the non-obese diabetic (NOD) mouse, a spontaneous model of autoimmune insulin-dependent diabetes (IDDM) that bears a remarkable resemblance to the human disease, has had an enormous impact on our understanding of the pathogenesis of IDDM. This is further enhanced by the ability to overexpress or knockout specific genes in these animals to test hypotheses related to the expression of, or protection against disease. Although a number of DERC investigators are actively engaged in research dependent on NOD mice, there has been no common resource that makes these unique animals generally available to the diabetes research community of Yale. Moreover, the Transgenic Core has been successful in providing DERC investigators with a variety of novel transgenic and gene knockout mice that must be bred to achieve a NOD genetic background. For example, it is not currently possible to produce gene knockouts in NOD mice. Thus, the task of breeding animals and testing for NOD background genes has been left to individual investigators, a task which is labor-intensive and very costly. As a result, the Executive Committee as well as the external Advisory Committee strongly endorsed the proposal to establish a new Core for this purpose. Limited funding (specifically J. Rife, at 25% effort) was provided in the current year to establish the Core with plans to expand its activities in the next grant cycle. It is the goal of the DERC to offer DERC members with access to an effective facility and unique animal resources so that research can be performed more efficiently as well as at a major cost savings. The animal genetics and breeding core is an essential resource for the work of the Yale Diabetes Endocrinology Research Center (Y-DERC). The core will provide DERC investigators with NOD mice which have been carefully bred and housed in a specific pathogen free environment to give a high incidence of diabetes, 90% in females and 65% in males by the age of six months. We have also developed a number of transgenic and gene knockout strains on the NOD genetic background by introgressively back crossing these strains of mice to NOD core stock. In addition, some transgenic strains have been generated by direct injection of transgene DNA into the ova of NOD mice and in these strains, extensive back crossing is not necessary. Finally, the core also maintains congenic NOD strains that serve as controls for experiments that require NOD genetic background but different MHC as well as strains that can serve as controls for the NOD MHC which is H2g7. The objective of this Core is to make this unique animal resource available to Center investigators.
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