Generation and analysis of mice lacking the prostanoid receptor

我们构建了与前列腺素受体基因的八种类型和亚型中的每一种同源重组的靶向载体。将载体导入源自小鼠品系129/奥拉的ES细胞中。然后将注射ES细胞的囊胚导入假孕ICR小鼠的子宫中，产生嵌合小鼠。将嵌合小鼠与C57 BL/6小鼠杂交，产生F1小鼠，然后产生缺乏每种前列腺素受体的F2小鼠。我们尝试将这些突变小鼠分别与C57 BL/6、balb/c和DBA 1小鼠进行回交，以获得同源小鼠，通过对这些缺失前列腺素受体的小鼠的分析，揭示了前列腺素受体在体内的新的生理和病理生理作用。PGI_2具有增加血管通透性、传递炎症痛感和抗血栓形成的作用。PGF_1<2alpha>通过诱导黄体消退降低血浆孕酮水平，进而上调子宫催产素受体的表达。PGE_2作用于EP_4受体，调节动脉导管的功能，这一结果将有助于开发特异性作用于前列腺素受体的新药，并为该类药物的应用提供线索。

We constructed the targeting vectors for homologous recombination with each of the eight rypes and subtypes of the prostanoid receptor genes. The vectors were introduced into the ES cells originating from the mouse strain of 129/ola. The blastcystes injected with the ES cells were then intoduced into the uterus of pseudo-pregnant ICR mice, and the chimeric mice were generated. The chimeric mice were crossed with C57BL/6 mice, and the F1 mice were generated followed by F2 mice lacking each of the prostanoid receptor. We have been trying to back-cross each of the mutant mice to C57BL/6, balb/c and DBA1 mice to get the congenic mice.Analyzes of these mice lacking each of the prostanoid receptors have revealed the novel physiological and pathophysiological roles of prstanoids in the body. PGI_2 has roles in increased vascular permiability and transmission of pain sensation in inflammation as well as antithrombotic role. PGF_<2alpha> decreases the plasma progesterone level by inducing the regression of corpus luteum, which then upregulates the expression of the oxytosin receptors in the uterus at term. PGE_2 acts on the EP4 receptor and regulates the function of the ductus arteriosus.These results would contribute to the development of new drugs acting specifically on each prostanoid receptors, and would also present the clues to the application of these drugs.