Ledent C, Coppée F, Dumont J E, Vassart G, Parmentier M
IRIBHN, Université Libre de Bruxelles, Belgium.
Exp Clin Endocrinol Diabetes. 1996;104 Suppl 3:43-6. doi: 10.1055/s-0029-1211683.
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 RB1 (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 RB1 and related proteins in the negative control of proliferation that characterizes thyroid cells in the adult. Other transgenic models of thyroid diseases are discussed.
构建了发生甲状腺疾病的小鼠转基因模型。所有转基因均由甲状腺球蛋白基因的甲状腺特异性启动子驱动。通过使用细菌氯霉素乙酰转移酶基因作为报告基因来研究启动子的组织特异性。腺苷A2a受体的表达导致cAMP级联反应的持续激活。结果，转基因小鼠出现严重的甲状腺功能亢进和巨大甲状腺肿，在体内证明了cAMP级联反应在促进甲状腺细胞功能和增殖中的作用。这些小鼠构成了自主性高功能腺瘤和非自身免疫性家族性甲状腺功能亢进的模型，其中突变的促甲状腺激素受体持续刺激cAMP级联反应。在另一个转基因模型中，人乳头瘤病毒16型的E7癌蛋白的表达抑制了视网膜母细胞瘤易感基因产物RB1（及相关蛋白）的功能。结果是出现了分化良好且功能正常的胶样甲状腺肿，并逐渐发展为分化型恶性病变。该模型表明RB1及相关蛋白在成年甲状腺细胞增殖的负调控中起重要作用。还讨论了其他甲状腺疾病的转基因模型。
