Thyroid Hormone Action: Insight from Transgenic Mouse Models
Thyroid Hormone Action: Insight from Transgenic Mouse Models
复制标题
甲状腺激素作用：转基因小鼠模型的见解
DOI：
--
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发表时间：
2003
影响因子：
2.6
通讯作者：
F. Wondisford
中科院分区：
文献类型：
--
作者：
F. Wondisford
甲状腺激素受体（TRs）是病毒性成红细胞白血病癌基因（v-erbA）的细胞同源物。TRs（c-crbA同种型）来源于哺乳动物中两个独立的基因座：α和β。通过在小鼠中进行的一系列敲除实验，其中一种或几种TR亚型被删除，已经证明TR-β亚型控制促甲状腺激素的中枢调节。在这些亚型中，TR-β2在介导下丘脑-垂体-甲状腺轴的负反馈控制中最重要。然而，对TR敲除动物的进一步分析显示，它们表现出比甲状腺功能减退动物温和得多的总体表型，表明受体损失不等同于体内配体损失。为了理解这一明显的矛盾，我们产生了表达来自TR-β等位基因的非T3结合受体（Δ 337 T）的动物。这些小鼠表现出完全的甲状腺功能减退表型，表明未配体的TR介导甲状腺功能减退的作用。由于该突变TR与核受体组成性结合，这也表明这类蛋白质是体内介导甲状腺功能减退症所必需的。
Thyroid hormone receptors (TRs) are cellular homologues of the viral erythroblastic leukemia oncogene (v-erbA). TRs (c-crbA isoforms) are derived from two separate gene loci in mammals: α and β. Through a series of knockout experiments in mice in which one or several of the TR isoforms were deleted, it has been demonstrated that the TR-β isoforms control central regulation of thyroid-stimulating hormone. Of these isoforms, TR-β2 is the most important in mediating negative feedback control of the hypothalamic-pituitary-thyroid axis. Further analysis of TR knockout animals revealed, however, that they exhibited a much milder overall phenotype than hypothyroid animals, indicating that receptor loss was not equivalent to ligand loss in vivo. To understand this apparent paradox, we generated animals expressing a non-T3 binding receptor (Δ337T) from the TR-β allele. These mice displayed a complete hypothyroid phenotype, demonstrating that the unliganded TR mediates the effect of hypothyroidism. Because this mutant TR constitutively binds to nuclear coreprssors, it also suggests that this class of proteins is essential for mediating hypothyroidism in vivo.
影响因子：
4
作者：
Kristen Jepsen;M. Rosenfeld
通讯作者：
Kristen Jepsen;M. Rosenfeld
患有全身性甲状腺激素抵抗的患者中 c-erbA β 甲状腺激素受体基因的纯合缺失：突变受体的分离和表征。
DOI：
10.1210/mend-5-3-327
发表时间：
1991
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Usala,SJ;Menke,JB;Watson,TL;Wondisford,FE;Weintraub,BD;Berard,J;Bradley,WE;Ono,S;Mueller,OT;Bercu,BB
通讯作者：
Bercu,BB