小鼠中Runx2缺乏会导致甲状腺球蛋白表达降低和甲状腺功能减退。
Runx2 deficiency in mice causes decreased thyroglobulin expression and hypothyroidism.
作者信息
Endo Toyoshi, Kobayashi Tetsuro
机构信息
Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo City, Yamanashi 409-3898, Japan.
出版信息
Mol Endocrinol. 2010 Jun;24(6):1267-73. doi: 10.1210/me.2010-0056. Epub 2010 Apr 7.
Abstract
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.
摘要
我们最近报道了成骨细胞特异性转录因子Runx2（Cbfa1/AML3）在人甲状腺乳头状癌组织中的过表达。我们在此报告，正常甲状腺细胞也表达Runx2，且Runx2(+/-)小鼠处于甲状腺功能减退状态。为阐明其机制，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水平对钠/碘同向转运体mRNA的量没有影响，但显著降低了甲状腺球蛋白（Tg）mRNA的量。Tg基因启动子上存在Runx2结合共有序列，凝胶迁移试验表明Runx2与该区域结合。报告基因试验表明，该区域的缺失或结合位点的突变显著损害启动子功能。这些结果表明，小鼠中Runx2缺乏导致Tg表达降低和一种新型的甲状腺功能减退。
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