Analysis of labor onset by construction of oxytocin receptor deficient mice

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The major endocrine function of OT is uterotonic action at parturition and milk ejection. In addition. OT affects the regulation of ovarian function as well as sexual, social and maternal behaviors through central nervous system. To determine the structure of the mouse oxytocin receptor (OTR) gene, we have screened a mouse genomic library and confirmed cDNA sequence. The predicted amino acid sequence is 91% identical to human OTR.The gene contains 4 exons and 3 introns. Exons 1 and 2 contain the 5'untranslated region, with exons 3 and 4 encoding the amino acids of the receptor. The promoter region contains multiple putative interleukin-response elements and estorgen responsive elements. Expression of OTR gene in the uterus during pregnancy reached maximum at day 20 of gestation. The information obtained from the mouse OTR gene facilitates further comparative and biochemical analysis for protein structure-function relationships and gene regulatory mechanisms (published in Mol.Cell.Endocrinol.127 ; 25-32 1996) The rodent model system has considerable practical advantages over other mammalian species. Our analysis of the mouse OTR gene provides a basis for the elucidation of the molecular mechanisms underlying OTR gene expression and, of the unresolved question as to whether mechanisms trigger the onset of parturition under phsiological and pathophysiological conditions. Mice deficient in oxytocin receptor are now under construction using embryonic stem cell technology.