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2772186 
Journal Article 
Transgenic Insulin (B:9-23) T-Cell Receptor Mice Develop Autoimmune Diabetes Dependent Upon RAG Genotype, H-2 super(g7) Homozygosity, and Insulin 2 Gene Knockout 
Jasinski, JM; Yu, L; Nakayama, M; Li, MM; Lipes, MA; Eisenbarth, GS; Liu, E 
2006 
Yes 
Diabetes
ISSN: 0012-1797
EISSN: 1939-327X 
American Diabetes Association, 1701 N. Beauregard St. Alexandria VA 22311 USA, [mailto:customerservice@diabetes.org], [URL:http://www.diabetes.org] 
55 
7 (Jul 2006) 
1978-1984 
English 
16804066 
WOS:000238764600010 
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 super(-/-) (backcross 1 generation). Disease progression is heterogeneous and is modified by a series of genetic factors including heterozygosity (H-2 super(g7)/H-2 super(q)) versus homozygosity for H-2 super(g7), the presence of additional T-/B-cell receptor-rearranged genes (RAG super(+) versus RAG super(-/-)), and the insulin 2 gene knockout (the insulin gene expressed in the NOD thymus). Despite lymphopenia, 40% of H-2 super(g7/g7) BDC12-4.1 TCR super(+) RAG super(-/-) Ins2 super(-/-) mice are diabetic by 10 weeks of age. As few as 13,500 transgenic T-cells from a diabetic TCR super(+) RAG super(-/-) 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. 
T-cell receptor; Autoimmunity; Autoimmune diseases; Insulitis; ^AT-cell receptor; Lymphopenia; Thymus; Lymphocytes T; Heterozygosity; Histocompatibility antigen H-2; Insulin; Beta cells; Diabetes mellitus