Runx2 deficiency in mice causes decreased thyroglobulin expression and hypothyroidism.
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.
Endo
Toyoshi
T
Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo City, Yamanashi 409-3898, Japan. endot@yamanashi.ac.jp
Kobayashi
Tetsuro
T
D000818:Animals; D050659:Core Binding Factor Alpha 1 Subunit / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D007037:Hypothyroidism / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D013954:Thyroglobulin / Q000235:genetics / Q000378:metabolism*; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology
D050659:Core Binding Factor Alpha 1 Subunit; D034741:RNA, Small Interfering; C493716:Runx2 protein, mouse; D013954:Thyroglobulin