Analysis of labor onset by construction of oxytocin receptor deficient mice

OT的主要内分泌功能是在分娩和泌乳时的子宫张力作用。此外。OT通过中枢神经系统影响卵巢功能以及性行为、社交行为和母性行为的调节。为了确定小鼠催产素受体（OTR）基因的结构，我们筛选了小鼠基因组文库并确定了cDNA序列。预测的氨基酸序列与人类OTR相同91%。该基因包含4个外显子和3个内含子。外显子1和2包含5'非翻译区，外显子3和4编码受体的氨基酸。启动子区域包含多个假定的白介素反应元件和雌激素反应元件。妊娠期间子宫中OTR基因的表达在妊娠第20天达到最大值。从小鼠OTR基因中获得的信息有助于进一步对蛋白质结构功能关系和基因调控机制进行比较和生化分析（发表于Mol.Cell.Endocrinol）。127年;（25-32 1996）啮齿动物模型系统与其他哺乳动物相比具有相当大的实际优势。我们对小鼠OTR基因的分析为阐明OTR基因表达的分子机制以及在生理和病理生理条件下是否触发分娩的未解决问题提供了基础。目前正在利用胚胎干细胞技术构建缺乏催产素受体的小鼠。

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.