Thyroid RDC8 versus C57Bl6. Mus musculus

Mutations of the thyrotropin receptor leading to constitutive activation of the cAMP cascade are responsible for the development of hot nodules, if arising in a somatic cell, and non-auto-immune hyperthyroidism, when occurring in a germinal cell. An animal model of constitutive activation of the thyroid cAMP cascade has been obtained by generating transgenic mice expressing the adenosine receptor (Tg-A2aR) under the control of the thyroglobulin promoter. These mice develop huge goiters and die prematurely due to hyperthyroidism induced cardiac failure. To identify new genes involved in the tumorigenic pathway of the thyroid, we designed a protocol using microarray technology to study the differential expression, between normal and transgenic thyroid, of +/- 13.000 genes. 360 genes or EST showed a strong modulation with background corrected values of fluorescence superior to 2 fold change. The modulated genes were classified according to their proposed gene ontology functions. Approximately half of them were upregulated. The function of the majority of these genes in thyroid physiology is still to be determined. Some of them, like IGF-I, IGF-BP3, IGF-BP5, may play an important role in the development of thyroid nodules through paracrine mechanisms. Keywords = Thyroid Keywords = Adenosine Receptor 2a Keywords: parallel sample

促甲状腺激素受体（thyrotropin receptor）的突变若发生于体细胞，可导致cAMP级联反应组成型激活，进而引发热结节；若突变发生于生殖细胞，则会引起非自身免疫性甲状腺功能亢进症。
通过在甲状腺球蛋白（thyroglobulin）启动子的调控下表达腺苷受体（adenosine receptor）A2a亚型，研究人员成功构建了组成型激活甲状腺cAMP级联反应的转基因小鼠模型（Tg-A2aR）。该类小鼠会出现巨大甲状腺肿，并因甲状腺功能亢进引发的心力衰竭而过早死亡。
为鉴定参与甲状腺致瘤通路的新基因，本研究设计了基于微阵列（microarray）技术的实验方案，用于比较正常甲状腺与转基因甲状腺之间约13000个基因的差异表达情况。经背景校正后，共有360个基因或表达序列标签（expressed sequence tag, EST）表现出显著的表达调控，其荧光信号校正值的变化倍数大于2倍。
研究人员根据基因本体（Gene Ontology, GO）功能对这些受调控的基因进行了分类，其中约半数基因呈现上调表达。目前这类基因中多数在甲状腺生理过程中的功能仍有待明确。部分基因如胰岛素样生长因子-I（IGF-I, insulin-like growth factor I）、胰岛素样生长因子结合蛋白3（IGF-BP3, insulin-like growth factor binding protein 3）、胰岛素样生长因子结合蛋白5（IGF-BP5, insulin-like growth factor binding protein 5），可能通过旁分泌（paracrine）机制在甲状腺结节的发生发展中发挥重要作用。
关键词：甲状腺（Thyroid）
关键词：腺苷受体2a（Adenosine Receptor 2a）
关键词：平行样本（parallel sample）