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Development and Characterization of T cell Specific Insulin Receptor Transgenic Mouse Model To Study Type‐1 Diabetes
Author(s) -
Gupta Nirdesh K.,
Bretz James D.,
McInerney Marcia F.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1074.30
Subject(s) - insulitis , nod mice , nod , islet , t cell , pancreas , biology , endocrinology , insulin , medicine , microbiology and biotechnology , receptor , diabetes mellitus , immunology , immune system
In the nonobese diabetic (NOD) mouse, type1 diabetes (T1D) is an autoimmune disease characterized by insulitis and T cell‐mediated destruction of pancreatic islet â cells. The importance of insulin receptor (IR) expression in the pathogenesis of diabetes was examined since it was shown that IR is a chemotactic receptor capable of directing cell movement in response to insulin. Our published data shows that IR High/+ T cells aggressively transfer insulitis and diabetes while IR Low/− T cells are capable of neither. Therefore, IR may function to deliver T cells to the islet. Recently, it has been shown in NOD mice that benign insulitis can occur in the absence of T cell‐MHC/Ag interactions. The object of this work is to test whether T cells overexpressing IR, can move into the pancreas based on insulin chemotaxis alone, without being targeted to the pancreas by antigenic specificity. To that end a transgenic mouse is made wherein FLAG tagged IR expression is targeted to all T cells. If IR expression is a mechanism to move T cells into the islet then down regulation of IR expression or blocking of chemotactic IR activity specifically in T cells, will provide a new therapeutic target to block cell movement into the pancreas, thus preventing diabetes.