Generation and analysis of mice lacking the prostanoid receptor

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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.