致畸量视黄酸对小鼠胚胎Foxc2基因表达的影响

发布时间：2018-02-16 01:05

本文关键词： Foxc2 视黄酸小鼠胚胎发育　出处：《吉林大学》2009年硕士论文　论文类型：学位论文

【摘要】： 小鼠叉头框-c2(Forkhead Box c2,Foxc2)是进化上高度保守,具有DNA结合域的翼状螺旋转录因子超家族中的一员。人类FOXC2和鼠Foxc2有95%以上的同源性,其DNA结合域forkhead由100个氨基酸组成。在人类,FOXC2基因的变异可以引起淋巴水肿-双行睫综合征的发生,另外肥胖、脂质代谢、胰岛素抵抗和2型糖尿病等也与FOXC2基因的变异有关。对小鼠的研究已经证实,Foxc2在胚胎正常发育过程中是必不可少的。维生素A代谢产物视黄酸(Retinoic acid,RA)具有广泛的生物学功能,为胚胎发育中调节基因表达、细胞增殖与分化所必需,而过量视黄酸也会导致胚胎发育畸形。视黄酸信号途径主要通过胞内核受体RAR和RXR与配体结合,形成转录活化因子后与靶基因的视黄酸反应元件(RARE)相作用来活化或抑制基因表达,以此调控细胞增殖与分化。 Foxc2基因在小鼠胚胎中的表达是否受到视黄酸信号调节尚未见报道。为探讨二者在胚胎发育过程中的相互关系,研究视黄酸信号途径与Foxc2基因表达的关系,本实验通过免疫组化的方法,对摄入致畸剂量视黄酸后的小鼠胚胎中Foxc2基因表达程度进行了分析。实验结果显示,经外源性视黄酸作用后的小鼠胚胎心脏、眼、骨骼和内耳等部位的Foxc2蛋白表达量与正常小鼠胚胎呈现显著性差异,中毒剂量的视黄酸可明显降低Foxc2蛋白表达量。实验结果提示Foxc2基因在小鼠胚胎中的表达可能受到视黄酸信号途径的调控,但其作用机制仍需进一步研究证实。
[Abstract]:Mouse forkhead Box c2Foxc2) is a member of the superfamily of winglike helical transcription factors with highly conserved DNA binding domain. Human FOXC2 and mouse Foxc2 share more than 95% homology. Its DNA binding domain, forkhead, consists of 100 amino acids. Mutations in the FOXC2 gene in humans can cause lymphedema-double ciliary syndrome, obesity, and lipid metabolism. Insulin resistance and type 2 diabetes are also related to the variation of FOXC2 gene. Retinoic acid (Retinoic acid), a metabolite of vitamin A, has a wide range of biological functions, which is necessary for regulating gene expression, cell proliferation and differentiation in embryonic development. Excessive retinoic acid also leads to fetal malformation. Retinoic acid signaling pathway binds to ligands mainly through the cellular nuclear receptors RAR and RXR. Transcriptional activators are formed to activate or inhibit gene expression and regulate cell proliferation and differentiation through interaction with target gene retinoic acid response element (Rare). Whether the expression of Foxc2 gene in mouse embryos is regulated by retinoic acid signal has not been reported. In order to study the relationship between retinoic acid signaling pathway and Foxc2 gene expression in embryonic development, the relationship between retinoic acid signaling pathway and Foxc2 gene expression has been studied. The expression of Foxc2 gene in mouse embryos exposed to teratogenic doses of retinoic acid was analyzed by immunohistochemical method. The results showed that the mouse embryonic hearts and eyes were treated with exogenous retinoic acid. The expression of Foxc2 protein in bone and inner ear was significantly different from that in normal mouse embryos. The results suggested that the expression of Foxc2 gene in mouse embryos might be regulated by retinoic acid signaling pathway, but its mechanism should be further studied.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R321

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