Summary
Mouse transgenic models that develop thyroid diseases were generated. All transgenes
were driven by the thyroid specific promoter of the thyroglobulin gene. The tissue
specificity of the promoter was investigated by using the bacterial chloramphenicol
acetyl transferase gene as reporter. The expression of an adenosine A2a receptor resulted
in the permanent activation of the cAMP cascade. As a consequence, the transgenic
mice developed severe hyperthyroidism and a large goiter, demonstrating in vivo the
role of the cAMP cascade in the promotion of both function and proliferation of the
thyroid cell. These mice constitute a model for autonomous hyperfunctional adenoma
and non-autoimmune familial hyperthyroidism, where mutant thyrotropin receptors stimulate
the cAMP cascade constitutively. In another transgenic model, the function of the
retinoblastoma susceptibility gene product RBI (and of related proteins) was inhibited
by expression of the E7 oncoprotein of human papillomavirus type 16. The result was
the development of a differentiated and normofunctional colloid goiter, with the progressive
development of differentiated malignant lesions. This model suggests the essential
role of RBI and related proteins in the negative control of proliferation that characterizes
thyroid cells in the adult. Other transgenic models of thyroid diseases are discussed.
Key words
Transgenic mice - thyroid cancer - constitutive activity - retinoblastoma susceptibility
gene - G protein-coupled receptor
