The T3R alpha gene encoding a thyroid hormone receptor is essential for post-natal development and thyroid hormone production
The T3R alpha gene encoding a thyroid hormone receptor is essential for post-natal development and thyroid hormone production
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DOI：
10.1093/emboj/16.14.4412
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发表时间：
1997-07-16
期刊：
影响因子：
11.4
通讯作者：
Samarut, J
中科院分区：
文献类型：
--
作者：
Fraichard, A;Chassande, O;Samarut, J
甲状腺激素的多种功能被认为是由两种核受体介导的，T3R α 1和T3R β，分别由基因T3R α和T3R β编码。T3R α基因还产生非配体结合蛋白T3R α 2。这些受体的体内功能仍不清楚，我们在这里描述了T3R α基因的纯合失活，其消除了T3R α 1和T3R α 2同种型的产生，并导致小鼠在出生后5周内死亡，在出生后2周，纯合小鼠变得进行性甲状腺功能减退并表现出生长停滞，小肠和骨骼显示出强烈的延迟成熟，与T3R β基因对甲状腺激素产生的负调节功能相反，我们的数据表明T3R α基因产物参与了断奶时甲状腺激素产生的上调，因此，甲状腺激素的产生可能通过阳性T3R α和阴性T3R β途径来平衡。在纯合突变小鼠上观察到的异常表型强烈提示T3R α基因对于依赖母亲的幼鼠向“成年”小鼠的转化是必需的，这些数据定义了出生后发育期间甲状腺激素通过T3R α途径的重要体内功能。
The diverse functions of thyroid hormones are thought to be mediated by two nuclear receptors, T3R alpha 1 and T3R beta, encoded by the genes T3R alpha and T3R beta respectively. The T3R alpha gene also produces a non-ligand-binding protein T3R alpha 2. The in vivo functions of these receptors are still unclear, We describe here the homozygous inactivation of the T3R alpha gene which abrogates the production of both T3R alpha 1 and T3R alpha 2 isoforms and that leads to death in mice within 5 weeks after birth, After 2 weeks of life, the homozygous mice become progressively hypothyroidic and exhibit a growth arrest, Small intestine and bones showed a strongly delayed maturation, In contrast to the negative regulatory function of the T3R beta gene on thyroid hormone production, our data show that the T3R alpha gene products are involved in up-regulation of thyroid hormone production at weaning time, Thus, thyroid hormone production might be balanced through a positive T3R alpha and a negative T3R beta pathway, The abnormal phenotypes observed on the homozygous mutant mice strongly suggest that the T3R alpha gene is essential for the transformation of a mother-dependent pup to an 'adult' mouse, These data define crucial in vivo functions for thyroid hormones through a T3R alpha pathway during post-natal development.