Runx2 Deficiency in Mice Causes Decreased Thyroglobulin Expression and Hypothyroidism
Runx2 Deficiency in Mice Causes Decreased Thyroglobulin Expression and Hypothyroidism
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DOI：
10.1210/me.2010-0056
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发表时间：
2010-06-01
影响因子：
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通讯作者：
Kobayashi, Tetsuro
中科院分区：
文献类型：
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作者：
Endo, Toyoshi;Kobayashi, Tetsuro
我们最近报道了 Runx2 (Cbfa1/AML3)（一种成骨细胞特异性转录因子）在人乳头状甲状腺癌组织中的过度表达。我们在此报告，正常甲状腺细胞也表达 Runx2，并且 Runx2(+/-) 小鼠处于甲状腺功能减退状态。为了阐明这一机制，我们研究了小干扰RNA介导的Runx2沉默对FRTL-5细胞中甲状腺特异性基因表达的影响。降低 Runx2 的水平对 Na+/I- 同向转运体 mRNA 的量没有影响，但显着降低甲状腺球蛋白 (Tg) mRNA 的量。 Runx2 结合共有序列存在于 Tg 基因启动子上，凝胶迁移测定显示 Runx2 与该区域结合。报告基因检测表明，删除该区域或在结合位点引入突变会显着损害启动子功能。这些结果表明，小鼠 Runx2 缺陷会导致 Tg 表达减少和新型甲状腺功能减退症。 （分子内分泌学24：1267-1273，2010）
We recently reported on the overexpression of Runx2 (Cbfa1/AML3), an osteoblast-specific transcription factor, in human papillary thyroid cancer tissues. We report here that normal thyrocytes also express Runx2 and that Runx2(+/-) mice are in a hypothyroid state. To clarify the mechanism, we studied the effects of small interfering RNA-mediated silencing of Runx2 on thyroid-specific gene expression in FRTL-5 cells. Lowering the levels of Runx2 had no effect on the amount of Na+/I- symporter mRNA but markedly decreased the amount of thyroglobulin (Tg) mRNA. A Runx2 binding consensus sequence is present on the Tg gene promoter, and gel-shift assay revealed that Runx2 binds to this region. Reporter assay showed that deletion of the region or introduction of a mutation into the binding site significantly impairs promoter function. These results indicate that Runx2 deficiency in mice causes decreased Tg expression and a novel type of hypothyroidism. (Molecular Endocrinology 24: 1267-1273, 2010)