A transgenic model for studying islet development.
The regeneration of islet cells in a transgenic mouse strain harboring the interferon-gamma gene (IFN-gamma) linked to the insulin promoter DNA fragment (ins-IFN-gamma) is described. The regeneration follows the loss of islets by an immune response provoked by IFN-gamma and manifests in the proliferation of duct cells, the presence of progenitor cells, and the formation of buds and isletlike structure. All three types (A, B, and D) of four endocrine cells identified by immunolabeling are present. The progenitor cells express neuronal enzymes, tyrosine hydroxylase (TH) and glutamic acid decarboxylase (GAD), as revealed by specific antibodies. The results indicate that the islet regeneration closely resembles the embryonic islet differentiation and serves as a model for studying islet development. The expression of neuronal enzymes by islet progenitor cells signifies yet unknown relationships to the nervous tissue. GAD, recognized as an autoantigen in insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome, may provide a clue to the mechanism of autoimmune disease.
Gu
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D
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
Sarvetnick
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N
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000502:physiology; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology; D007515:Islets of Langerhans / Q000196:embryology / Q000254:growth & development*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008954:Models, Biological; D009024:Morphogenesis
D007328:Insulin; D007371:Interferon-gamma