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- Title
Long-term prevention of diabetes and marked suppression of insulin autoantibodies and insulitis in mice lacking native insulin B9-23 sequence.
- Authors
Nakayama, M; Babaya, N; Miao, D; Gianani, R; Liu, E; Elliott, J F; Eisenbarth, G S
- Abstract
We analyzed double native insulin gene knockout NOD mice with a mutated (B16:alanine) proinsulin transgene at multiple ages for the development of insulin autoantibodies, insulitis, and diabetes. In contrast to mice with at least one copy of a native insulin gene that expressed insulin antibodies, only 2 out of 21 (10%) double native insulin gene knockout mice with a mutated insulin transgene developed insulin autoantibodies. Of 21 double insulin knockout mice sacrificed between 10 to 48 weeks of age, only 5 showed minimal insulitis versus 100% of wild-type NOD and more than 90% of insulin 1 knockout mice. Consistent with robust suppression of insulin autoantibodies and insulitis, no double insulin knockout mice developed diabetes. In that the B9-23 peptide with B16A is an altered peptide ligand inducing Th2 responses, we analyzed transfer of splenocytes into NOD.SCID mice. There was no evidence for regulatory T cells able to inhibit transfer of diabetes by diabetogenic NOD splenocytes. Insulin peptide B9-23 is likely a crucial target for initiation of islet autoimmunity and further mutation of the sequence will be tested to attempt to eliminate all anti-islet autoimmunity.
- Publication
Annals of the New York Academy of Sciences, 2006, Vol 1079, p122
- ISSN
0077-8923
- Publication type
Journal Article
- DOI
10.1196/annals.1375.018