A Track Record on SHOX: From Basic Research to Complex Models and Therapy.
A Track Record on SHOX: From Basic Research to Complex Models and Therapy.
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SHOX的记录：从基础研究到复杂的模型和治疗。
DOI：
10.1210/er.2016-1036
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发表时间：
2016-08
影响因子：
20.3
通讯作者：
Rappold GA
中科院分区：
文献类型：
--
作者：
Marchini A;Ogata T;Rappold GA
Shox缺乏症是最常见的遗传性生长障碍，与孤立和综合征型的矮小有关。由同源框基因Shox突变引起，其各种临床表现包括孤立性矮小、L-威尔氏软骨发育不良和朗格中髓发育不良。此外，Shox缺乏与Turner综合征的骨骼特征有关。致病的Shox突变使下游病理与明确的分子损伤有关。Shox的表达水平受到严格调控，几乎一半的致病突变影响了增强子。Shox缺乏症的临床严重程度因性别不同而不同，范围从正常身材到深度中胚骨发育不良。Shox缺乏症儿童的治疗方案可供选择。二十年的研究支持Shox作为一种转录因子的概念，它整合了骨发育、生长板生物学和细胞凋亡的不同方面。由于在小鼠体内没有这种基因，动物模型的选择变成了鸡和斑马鱼。因此，这些模型与微团培养和原代细胞系一起被用于研究Shox的功能。途径和网络分析已经确定了相互作用因素、靶基因和调节因子。在这里，我们总结最新的数据，并深入了解Shox在矮小和肢体发育的发病机制中的关键分子和细胞功能。
SHOX deficiency is the most frequent genetic growth disorder associated with isolated and syndromic forms of short stature. Caused by mutations in the homeobox gene SHOX, its varied clinical manifestations include isolated short stature, Léri-Weill dyschondrosteosis, and Langer mesomelic dysplasia. In addition, SHOX deficiency contributes to the skeletal features in Turner syndrome. Causative SHOX mutations have allowed downstream pathology to be linked to defined molecular lesions. Expression levels of SHOX are tightly regulated, and almost half of the pathogenic mutations have affected enhancers. Clinical severity of SHOX deficiency varies between genders and ranges from normal stature to profound mesomelic skeletal dysplasia. Treatment options for children with SHOX deficiency are available. Two decades of research support the concept of SHOX as a transcription factor that integrates diverse aspects of bone development, growth plate biology, and apoptosis. Due to its absence in mouse, the animal models of choice have become chicken and zebrafish. These models, therefore, together with micromass cultures and primary cell lines, have been used to address SHOX function. Pathway and network analyses have identified interactors, target genes, and regulators. Here, we summarize recent data and give insight into the critical molecular and cellular functions of SHOX in the etiopathogenesis of short stature and limb development.
影响因子：
3.7
作者：
Durand C;Decker E;Roeth R;Schneider KU;Rappold G
通讯作者：
Rappold G