Center for Craniofacial Regeneration, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
College of Dentistry, The Ohio State University, Columbus, OH 43210, USA.
Genes (Basel). 2020 Jan 11;11(1):83. doi: 10.3390/genes11010083.
Human midfacial clefting is a rare subset of orofacial clefting and in severe cases, the cleft separates the nostrils splitting the nose into two independent structures. To begin to understand the morphological and genetic causes of midfacial clefting we recovered the mouse line. embryos develop a complete midfacial cleft through the lip, and snout closely modelling human midfacial clefting. The mouse line has ethylnitrosourea (ENU)-induced missense mutations in and . The mutations segregate with the cleft face phenotype. Importantly, the nasal cartilages and surrounding bones are patterned and develop normal morphology, except for the lateral displacement because of the cleft. We conclude that the midfacial cleft arises from the failure of the medial convergence of the paired medial nasal prominences between E10.5 to E11.5 rather than defective cell proliferation and death. Our work uncovers a novel mouse model and mechanism for the etiology of midfacial clefting.
人类面中部裂是口面裂中较为罕见的一种类型，在严重情况下，裂隙会将鼻孔分开，使鼻子分成两个独立的结构。为了开始了解面中部裂的形态和遗传原因，我们恢复了 小鼠品系。 胚胎通过唇裂形成完全的面中部裂隙，而口鼻部则非常类似于人类的面中部裂隙。 小鼠品系在 和 中具有乙基亚硝脲（ENU）诱导的错义突变。这些突变与裂隙面表型分离。重要的是，除了裂隙导致的外侧移位外，鼻软骨和周围骨骼的模式和发育形态正常。我们得出结论，面中部裂隙是由于 E10.5 至 E11.5 期间双侧内侧鼻突的内侧融合失败而不是细胞增殖和死亡缺陷引起的。我们的工作揭示了一种新的小鼠模型和面中部裂发病机制的新机制。
