Role of sex steroids in female TIEG-null mouse bone loss

描述（由申请人提供）：TGF-β诱导型早期基因-1（TIEG）是Kruppel样转录因子家族的成员，最初克隆自人成骨细胞，已知其在转录调控和TGF-β介导的Smad信号传导中发挥重要作用。TIEG在成骨细胞中被雌激素快速诱导，并且这种诱导似乎特异性地通过雌激素受体β的作用。通过TIEG基因缺失小鼠的开发和表征，我们已经表明，雌性动物相对于野生型同窝出生的小鼠显示出明显更弱、更小和更低密度的骨骼。有趣的是，在雄性动物中检测不到这些差异，这意味着性类固醇与TIEG表达的丧失结合在观察到的性别特异性骨表型中的作用。基于上述观察结果，本提案的目标是进一步表征性别特异性骨表型背后的分子基础，以确定雌激素和/或睾酮在这种性别特异性中的作用，并阐明雌激素受体β特异性诱导TIEG的机制。

DESCRIPTION (provided by applicant): TGF-beta inducible early gene-1 (TIEG) is a member of the Kruppel-like transcription factor family originally cloned from human osteoblasts that is known to play an important role in transcriptional regulation and in TGF-beta mediated Smad signaling. TIEG is rapidly induced by estrogen in osteoblast cells and this induction seems to be specifically through the action of estrogen receptor-beta. Through the development and characterization of TIEG-null mice, we have shown that female animals display significantly weaker, smaller and less dense bones relative to wild-type litter mates. Intriguingly, these differences are not detectable in male animals implying a role for the sex steroids, in combination with the loss of TIEG expression, in the observed gender specific bone phenotype. Based on the above observations, it is the goal of this proposal to further characterize the molecular basis behind the gender specific bone phenotype, to identify the role of estrogen and/or testosterone in this gender specificity and to elucidate the mechanisms by which TIEG is specifically induced by estrogen receptor-beta.