Lee Kevin K L, Stanier Philip, Pauws Erwin
UCL Great Ormond Street Institute of Child Health, London, UK.
Mol Syndromol. 2019 Feb;10(1-2):58-73. doi: 10.1159/000491004. Epub 2018 Jul 13.
Craniosynostosis is a common craniofacial birth defect. This review focusses on the advances that have been achieved through studying the pathogenesis of craniosynostosis using mouse models. Classic methods of gene targeting which generate individual gene knockout models have successfully identified numerous genes required for normal development of the skull bones and sutures. However, the study of syndromic craniosynostosis has largely benefited from the production of knockin models that precisely mimic human mutations. These have allowed the detailed investigation of downstream events at the cellular and molecular level following otherwise unpredictable gain-of-function effects. This has greatly enhanced our understanding of the pathogenesis of this disease and has the potential to translate into improvement of the clinical management of this condition in the future.
颅缝早闭是一种常见的颅面先天性缺陷。本综述聚焦于通过使用小鼠模型研究颅缝早闭的发病机制所取得的进展。经典的基因靶向方法可生成单个基因敲除模型，已成功鉴定出许多颅骨和颅缝正常发育所需的基因。然而，综合征性颅缝早闭的研究在很大程度上受益于精确模拟人类突变的敲入模型的构建。这些模型使得在细胞和分子水平上对原本不可预测的功能获得效应后的下游事件进行详细研究成为可能。这极大地增进了我们对该疾病发病机制的理解，并有可能在未来转化为改善该病的临床管理。
