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Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model
Published on: March 17, 2023
Thyroid gene expression in familial nonautoimmune hyperthyroidism shows common characteristics with hyperfunctioning
Aline Hébrant1, Jacqueline Van Sande, Pierre P Roger
1Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels, campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium.
The Journal of Clinical Endocrinology and Metabolism
|April 23, 2009
Summary
Activating mutations in the TSH receptor cause familial nonautoimmune hyperthyroidism (FNAH) and autonomous adenomas (AAs). While both conditions share similar molecular changes, somatic mutations in AAs have a more potent effect on thyroid cell phenotype than inherited FNAH mutations.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Familial nonautoimmune hyperthyroidism (FNAH) and hyperfunctioning autonomous adenomas (AAs) stem from activating mutations in the TSH receptor.
- FNAH results from inherited mutations affecting the entire thyroid gland, while AAs arise from somatic mutations in adulthood.
Purpose of the Study:
- To define and compare the functional and molecular phenotypes of FNAH and AAs.
- To investigate the impact of TSH receptor mutations on thyroid cell behavior.
Main Methods:
- In vitro functional studies of thyroid tissue slices and cultured thyrocytes.
- Gene expression profiling using microarray hybridization.
- Bioinformatic analysis of gene expression data.
Main Results:
- FNAH thyrocytes exhibited normal iodide metabolism and signaling but increased sensitivity to TSH.
- Gene expression analysis revealed shared molecular alterations between FNAH and AAs, with AAs showing unique gene regulations.
- Commonly downregulated genes in both conditions were related to immune response, cell adhesion, and apoptosis, while AAs showed upregulated pathways involved in biosynthesis.
Conclusions:
- Activating TSH receptor mutations, whether inherited (FNAH) or somatic (AAs), induce similar qualitative changes in thyroid cell phenotype.
- Somatic mutations in AAs exert a stronger effect on the thyroid cell phenotype compared to inherited FNAH mutations.
- FNAH and AAs represent distinct clinical manifestations of a single underlying disease: genetic hyperthyroidism.
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