Animal models of insulin-dependent diabetes.
Animal models have contributed enormously to study in the field of type 1 diabetes. Perhaps the most intensively studied model is the nonobese diabetic (NOD) mouse, which develops an autoimmune-mediated spontaneous diabetes associated with the development of insulin autoantibodies and insulitis. Accurate measurement of antiislet autoantibodies by radioassay and detection of antigen-specific T cells using major histocompatibility complex tetramers are possible. Various strategies have been developed in preventing diabetes in animal models; a peptide-induced model of type 1 diabetes has been described. Finally, the development of peptide vaccines is hampered by the risk of anaphylaxis in both mouse and humans. In this chapter, methods and strategies to measure antiinsulin autoantibodies, to detect antigen-specific T cells by tetramer analysis, and to prevent diabetes using peptide vaccines are discussed. Along with these topics, a protocol of peptide-induced diabetes and peptide vaccine-induced anaphylaxis are described, serving as a reminder of the potential dangers that could exist in human trials. In summary, animal models have become necessary in the study of type 1 diabetes and provide researchers important tools to conduct studies that could not otherwise be performed in humans.
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, CO, USA.
Edwin
E
Liu
Liping
L
Yu
Hiroaki
H
Moriyama
George S
GS
Eisenbarth
D000595:Amino Acid Sequence; D000707:Anaphylaxis / Q000209:etiology / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D004195:Disease Models, Animal; D006801:Humans; D007114:Immunization; D007328:Insulin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D007328:Insulin; D010446:Peptide Fragments; C097877:insulin B (9-23)