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Lessons from mouse models of Graves' disease
A Eckstein1, S Philipp2, G Goertz2
1Department of Ophthalmology, Medical Faculty, University Duisburg-Essen, Essen, Germany. anja.eckstein@uk-essen.de.
Abstract:
Graves' disease (GD) is an autoimmune condition with the appearance of anti-TSH receptor (TSHR) autoantibodies in the serum. The consequence is the development of hyperthyroidism in most of the patients. In addition, in the most severe cases, patients can develop orbitopathy (GO), achropachy and dermopathy. The central role of the TSHR for the disease pathology has been well accepted. Therefore immunization against the TSHR is pivotal for the creation of in vivo models for the disease. However, TSHR is well preserved among the species and therefore the immune system is highly tolerant. Many differing attempts have been performed to break tolerance and to create a proper animal model in the last decades. The most successful have been achieved by introducing the human TSHR extracellular domain into the body, either by injection of plasmid or adenoviruses. Currently available models develop the whole spectrum of Graves' disease-autoimmune thyroid disease and orbitopathy and are suitable to study disease pathogenesis and to perform treatment studies. In recent publications new immunomodulatory therapies have been assessed and also diseaseprevention by inducing tolerance using small cyclic peptides from the antigenic region of the extracellular subunit of the TSHR.
Insights
Developing animal models for Graves' disease (GD) is crucial for understanding hyperthyroidism. Researchers successfully created models by introducing the human TSHR, enabling new treatment studies.
Area of Science:
- Immunology
- Endocrinology
- Autoimmune Diseases
Background:
- Graves' disease (GD) is an autoimmune disorder characterized by anti-TSH receptor (TSHR) autoantibodies, leading to hyperthyroidism.
- Severe cases manifest with Graves' ophthalmopathy (GO), acropachy, and dermopathy.
- The TSHR is central to GD pathogenesis, making it a key target for disease modeling.
Purpose of the Study:
- To establish effective in vivo models for studying Graves' disease pathogenesis and evaluating treatments.
- To overcome immune tolerance to the conserved TSHR across species.
Main Methods:
- Immunization against the TSHR using strategies to break immune tolerance.
- Introduction of the human TSHR extracellular domain via plasmid or adenovirus vectors.
- Assessment of immunomodulatory therapies and disease prevention strategies.
Main Results:
- Successful development of animal models that replicate the full spectrum of Graves' disease, including autoimmune thyroid disease and orbitopathy.
- Current models are suitable for pathogenesis research and therapeutic intervention studies.
- Emerging research explores disease prevention through tolerance induction using TSHR-derived peptides.
Conclusions:
- Animal models expressing human TSHR are essential for advancing Graves' disease research.
- These models facilitate the study of disease mechanisms and the testing of novel therapeutic approaches.
- Future directions include developing tolerance-inducing strategies for disease prevention.
Related Concept Videos
01:28Graves' Disease I: Introduction
01:24Graves Disease II: Pathophysiology