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- Title
Transgenic Insulin (B:9-23) T-Cell Receptor Mice Develop Autoimmune Diabetes Dependent Upon RAG Genotype, H-2<sup>g7</sup> Homozygosity, and Insulin 2 Gene Knockout.
- Authors
Jasinski, Jean M.; Yu, Liping; Nakayama, Maki; Li, Marcella M.; Lipes, Myra A.; Eisenbarth, George S.; Liu, Edwin
- Abstract
A series of recent studies in humans and the NOD mouse model have highlighted the central role that autoimmunity directed against insulin, in particular the insulin B chain 9-23 peptide, may play in the pathogenesis of type 1 diabetes. Both pathogenic and protective T-cell clones recognizing the B:9-23 peptide have been produced. This report describes the successful creation of BDC12-4.1 T-cell receptor (TCR) transgenic mice with spontaneous insulitis in F1 mice (FVB x NOD) and spontaneous diabetes in NOD.RAG-/- (backcross 1 generation). Disease progression is heterogeneous and is modified by a series of genetic factors including heterozygosity (H-2g7/H-2q) versus homozygosity for H-2g7, the presence of additional T-/B-cell receptor-rearranged genes (RAG+ versus RAG-/-), and the insulin 2 gene knockout (the insulin gene expressed in the NOD thymus). Despite lymphopenia, 40% of H-2g7/g7 BDC12-4.1 TCR+ RAG-/- Ins2-/- mice are diabetic by 10 weeks of age. As few as 13,500 transgenic T-cells from a diabetic TCR+ RAG-/- mouse can transfer diabetes to an NOD.scid mouse. The current study demonstrates that the BDC12-4.1 TCR is sufficient to cause diabetes at NOD backcross 1, bypassing polygenic inhibition of insulitis and diabetogenesis. Diabetes 55: 1978-1984, 2006
- Publication
Diabetes, 2006, Vol 55, Issue 7, p1978
- ISSN
0012-1797
- Publication type
Academic Journal
- DOI
10.2337/db06-0058