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Published February 26, 1993 | public
Journal Article

Transgenic Mice That Express a Myelin Basic Protein-Specific T Cell Receptor Develop Spontaneous Autoimmunity


We constructed a transgenic mouse model that mimics the human autoimmune disease multiple sclerosis in its spontaneous induction and pathology. Transgenic mice were constructed expressing genes encoding a rearranged T cell receptor specific for myelin basic protein (MBP). T cell tolerance was not induced in the periphery, and functional, autoreactive T cells were found in the spleen and lymph nodes of these mice. Transgenic mice developed experimental allergic encephalomyelitis (EAE) following immunization with MBP and adjuvant plus pertussis toxin as well as with administration of pertussis toxin alone. Spontaneous EAE can develop in transgenic mice housed in a nonsterile facility but not in those maintained in a sterile, specific pathogen-free facility. This model system affords a unique opportunity to dissect the genetic and environmental variables that may contribute to the development of spontaneous autoimmune disease.

Additional Information

© 1993 by Cell Press. Received September 2, 1992; revised December 30, 1992. The authors thank R. A. Diamond and P. F. Koen at Caltech for expert technical assistance with flow cytometry. We also wish to thank E. Wilk and S. Marsh for technical assistance in analysis of the transgenic mice. We thank Dr. T. Hunkapiller for critical reading of the manuscript.

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