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Transgenic Expression of Mouse Proinsulin II Prevents Diabetes in Nonobese Diabetic Mice
Abstract
IDDM in humans and in nonobese diabetic (NOD) mice is a T-cell–dependent autoimmune disease in which the β-cells of the pancreatic islets are destroyed. Several putative β-cell autoantigens have been identified, but insulin and its precursor, proinsulin, are the only ones that are β-cell specific. (Pro)insulin may be a key autoantigen in IDDM. To address the role of proinsulin in the development of IDDM, we generated NOD mice transgenic for the mouse proinsulin II gene driven off a major histocompatibility complex (MHC) class II promoter to direct expression of the transgene to MHC class II bearing cells, including those in the thymus, with the aim of deleting proinsulin-reactive T-cells. The mononuclear cell infiltration of the islets (insulitis) is almost completely absent, and diabetes is prevented in these transgenic NOD mice. The mononuclear cell infiltration of the salivary glands (sialitis) and immune responses to ovalbumin (OVA) are not altered, indicating that the protective effect of the transgene is specific for islet pathology and not due to general immunosuppression. We conclude that autoimmunity to proinsulin plays a pivotal role in the development of IDDM.
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Cited by
Pugliese, A., Zeller, M., Fernandez, A., Zalcberg, L. J., Bartlett, R. J., Ricordi, C., Pietropaolo, M., Eisenbarth, G. S., Bennett, S. T., & Patel, D. D. (1997) · Nature Genetics · doi:10.1038/ng0397-293 · Cited by 945
Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice
Nakayama, M., Abiru, N., Moriyama, H., Babaya, N., Liu, E., Miao, D., Yu, L., Wegmann, D. R., Hutton, J. C., Elliott, J. F., et al. (2005) · Nature · doi:10.1038/nature03523 · Cited by 758
Autoimmune Destruction of Pancreatic β Cells
Yoon, J.-W., & Jun, H.-S. (2005) · American Journal of Therapeutics · doi:10.1097/01.mjt.0000178767.67857.63 · Cited by 308
Insulin Expression Levels in the Thymus Modulate Insulin-Specific Autoreactive T-Cell Tolerance
Chentoufi, A. A., & Polychronakos, C. (2002) · Diabetes · doi:10.2337/diabetes.51.5.1383 · Cited by 264
Chapter 4 CD8+ T Cells in Type 1 Diabetes
Tsai, S., Shameli, A., & Santamaria, P. (2008) · Advances in Immunology · doi:10.1016/s0065-2776(08)00804-3 · Cited by 140
Metadata
- Authors
- French, M. B., Allison, J., Cram, D. S., Thomas, H. E., Dempsey-Collier, M., Silva, A., Georgiou, H. M., Kay, T. W., Harrison, L. C., & Lew, A. M.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1997-01-01
- Volume
- 46
- Issue
- 1
- Pages
- 34-39
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2031426031
- Cited by
- 255
- References
- 0
- FWCI
- 7.85
- Type
- journal article
- Language
- en
- Open access
- closed
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- French, M. B., Allison, J., Cram, D. S., Thomas, H. E., Dempsey-Collier, M., Silva, A., Georgiou, H. M., Kay, T. W., Harrison, L. C., & Lew, A. M. (1997). Transgenic Expression of Mouse Proinsulin II Prevents Diabetes in Nonobese Diabetic Mice. Diabetes. https://doi.org/10.2337/diab.46.1.34
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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