The focus of our JDRF Autoimmunity Center is to create and study a humanized mouse model of Type 1 diabetes. The approach that we are developing involves use of immune deficient (γc-/-) mice with “knock-in” of human cytokine and other genes that are needed for optimal reconstitution with human cells. In addition, we have created transgenic mice that express human proinsulin in beta cells and in addition, have human MHC+ mouse MHC- mice in which the presentation and responses to human antigens (e.g. proinsulin, insulin) can be studied. We hope to reconstitute the immune deficient mice with human CD34+ bone marrow cells from patients with diabetes. The duration of diabetes should not be an issue so the use of nPOD tissue would be appropriate. We plan to study the ability of the reconstituted mice to develop diabetes – spontaneously or with provocateurs such as low dose streptozotocin, immunization with antigens, or even transgenic expression of B7.1 on beta cells. (adopted by nPOD staff)