Molecular mechanism of vitamin A and vitamin D actions

我们从维生素A和维生素D在完整动物体内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，它们只有在断奶后才发育。此外，将这些小鼠与RXRGamma Ko小鼠杂交，建立了VDR和RXRGamma的双Ko小鼠，表现出更多的表型，表明维生素A和维生素D之间存在交互作用。通过建立新的表达克隆系统，利用VDR Ko小鼠的表达cDNA文库，首次克隆了维生素D生物合成的关键酶--小鼠1α-羟基酶的基因。此外，我们还证明了该基因的遗传营养导致人类维生素D抵抗I型软骨病。

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.