Ellis Van Creveld2 is Required for Postnatal Craniofacial Bone Development.
Ellis Van Creveld2 is Required for Postnatal Craniofacial Bone Development.
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DOI：
10.1002/ar.23353
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发表时间：
2016-08
期刊：
影响因子：
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通讯作者：
Mochida Y
中科院分区：
文献类型：
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作者：
Badri MK;Zhang H;Ohyama Y;Venkitapathi S;Kamiya N;Takeda H;Ray M;Scott G;Tsuji T;Kunieda T;Mishina Y;Mochida Y
Ellis-van Creveld（EvC）综合征是一种EVC或EVC 2基因突变的遗传性疾病。以前的病例研究报告，EvC患者进行正畸治疗，表明颅面骨表型的存在。为了研究EVC 2基因中的突变是否引起颅面骨表型，产生Evc 2敲除（KO）小鼠并进行头影测量分析。制备野生型（WT）、杂合型（Het）和纯合型Evc 2 KO小鼠（1周龄、3周龄和6周龄）的头部，并基于侧位X射线照片上选择的参考点进行头影测量分析。然后计算线性和成角骨测量值，在WT、Het和KO之间进行比较，并在每个时间点进行统计学分析。我们的数据显示，KO中的颅面骨长度比WT和Het的颅面骨长度显著降低约20%，KO中某些骨骼的生长，包括鼻骨、腭长和前上颌骨的生长受到更多的影响，并且这些骨骼长度的减少在出生后较晚的时间点（3和6周）比早期时间点（1周）更显著。此外，骨与颅底和颅顶的关系在KO中发生了显著变化，即颅顶和鼻骨被压低，前颌骨和下颌骨向更腹侧方向发育。我们的研究是第一个显示Evc 2缺陷和EvC综合征颅面缺损之间的因果关系，证明Evc 2是颅面骨发育所必需的，其缺陷导致特定的面部骨生长缺陷。
Ellis-van Creveld (EvC) syndrome is a genetic disorder with mutations in either EVC or EVC2 gene. Previous case studies reported that EvC patients underwent orthodontic treatment, suggesting the presence of craniofacial bone phenotypes. To investigate whether a mutation in EVC2 gene causes a craniofacial bone phenotype, Evc2 knockout (KO) mice were generated and cephalometric analysis was performed. The heads of wild type (WT), heterozygous (Het) and homozygous Evc2 KO mice (1-, 3- and 6-week-old) were prepared and cephalometric analysis based on the selected reference points on lateral X-ray radiographs was performed. The linear and angular bone measurements were then calculated, compared between WT, Het and KO and statistically analyzed at each time point. Our data showed that length of craniofacial bones in KO was significantly lowered by ~20% to that of WT and Het, the growth of certain bones, including nasal bone, palatal length and premaxilla was more affected in KO, and the reduction in these bone length was more significantly enhanced at later postnatal time points (3 and 6 weeks) than early time point (1 week). Furthermore, bone-to-bone relationship to cranial base and cranial vault in KO was remarkably changed, i.e. cranial vault and nasal bone were depressed and premaxilla and mandible were developed in a more ventral direction. Our study was the first to show the cause-effect relationship between Evc2 deficiency and craniofacial defects in EvC syndrome, demonstrating that Evc2 is required for craniofacial bone development and its deficiency leads to specific facial bone growth defect.