Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation.
Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation.
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DOI：
10.1038/ncomms10328
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发表时间：
2016-01-21
影响因子：
16.6
通讯作者：
Trainor PA
中科院分区：
文献类型：
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作者：
Sakai D;Dixon J;Achilleos A;Dixon M;Trainor PA
颅面畸形约占所有出生缺陷的三分之一，是婴儿死亡的重要原因。由于构成头部和面部的大部分骨骼、软骨和结缔组织都来自称为神经嵴的多能迁移祖细胞群，因此颅面疾病通常归因于神经嵴细胞发育缺陷。Treacher柯林斯综合征（TCS）是一种颅面发育障碍，尽管TCS主要是通过TCOF 1的常染色体显性突变引起的，但没有明确的基因型-表型相关性。在这里，我们表明，Tcof 1单倍不足导致氧化应激诱导的DNA损伤和神经上皮细胞死亡。与这一发现相一致的是，母亲用抗氧化剂治疗可最大限度地减少神经上皮细胞的死亡，并显著改善或预防Tcof 1 +/−小鼠颅面异常的发病机制。因此，母亲的抗氧化剂膳食补充剂可能提供了一种途径，防止TCS和类似的neurocriticies的发病机制。 Treacher柯林综合征是一种先天性颅面综合征，TCOF 1基因发生突变。在这里，作者表明，Tcof 1功能丧失导致氧化应激诱导的DNA损伤和神经上皮细胞死亡，并且向怀孕的突变小鼠添加抗氧化剂可以保护这些缺陷。
Craniofacial anomalies account for approximately one-third of all birth defects and are a significant cause of infant mortality. Since the majority of the bones, cartilage and connective tissues that comprise the head and face are derived from a multipotent migratory progenitor cell population called the neural crest, craniofacial disorders are typically attributed to defects in neural crest cell development. Treacher Collins syndrome (TCS) is a disorder of craniofacial development and although TCS arises primarily through autosomal dominant mutations in TCOF1, no clear genotype–phenotype correlation has been documented. Here we show that Tcof1 haploinsufficiency results in oxidative stress-induced DNA damage and neuroepithelial cell death. Consistent with this discovery, maternal treatment with antioxidants minimizes cell death in the neuroepithelium and substantially ameliorates or prevents the pathogenesis of craniofacial anomalies in Tcof1+/− mice. Thus maternal antioxidant dietary supplementation may provide an avenue for protection against the pathogenesis of TCS and similar neurocristopathies. The TCOF1 gene is mutated in Treacher Collin's syndrome, a congenital craniofacial syndrome. Here, the authors show that Tcof1 loss-of-function results in oxidative stress induced DNA damage and neuroepithelial cell death, and addition of antioxidants to pregnant mutant mice protected against these defects.