Molecular mechanism of vitamin A and vitamin D actions

我们从维生素A和维生素D的核受体功能的角度研究了维生素A和维生素D作用的分子机制。我们培育了VDR KO小鼠，它们在断奶后才发育。将这些小鼠与RXRgamma Ko小鼠杂交，建立VDR和RXRgamma双Ko小鼠，小鼠表现出更多的过度表型，表明维生素a和维生素D之间存在交叉对话。利用新建立的VDR Ko小鼠表达cDNA文库，我们首次克隆了维生素D生物合成关键酶小鼠1 α -羟化酶的cDNA。此外，我们证明了该基因的遗传变异导致人类维生素D抗性I型佝偻病。

We studied the molecular mechanism of vitamin A and vitamin D actions in terms of function of their nuclear receptors in intact animals. We generated the VDR KO mice, and they developed only after weaning. Furtherrmore, those mice were crossed with RXRgamma Ko mice to establish double Ko mice for VDR and RXRgamma, and the mice exhibited more over phenotypes, indicating a cross-talk between vitamin A and vitamin D.By means of newly established expression cloning system with the expression cDNA libraly from VDR Ko mice, we cloned for the first time the cDNA of mouse 1alpha-hydroxylase, which is the key enzyme in Vitemin D biosynthesis. Moreover, we demonstrated that genetic nutaion in this gene causes Vitamin D resisttant type I rickets in human.