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Analysis of labor onset by construction of oxytocin receptor deficient mice

构建催产素受体缺陷小鼠的临产分析

基本信息

批准号：
07457387
负责人：
AZUMA Chihiro
金额：
$ 4.74万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

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.

催产素的主要内分泌功能是分娩时的子宫收缩和乳汁排出。另外。OT通过中枢神经系统影响卵巢功能的调节，并影响性行为、社会行为和母性行为。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认了cDNA序列。该基因由4个外显子和3个内含子组成，与人OTR的氨基酸序列同源性为91%。外显子1和2含有5 '非翻译区，外显子3和4编码受体的氨基酸。启动子区含有多个假定的白细胞介素反应元件和雌激素反应元件。OTR基因在妊娠期子宫中的表达在妊娠第20天达到高峰。从小鼠OTR基因获得的信息有助于对蛋白质结构-功能关系和基因调节机制进行进一步的比较和生物化学分析（发表于Mol.Cell.Endocrinol.127; 25-32 1996）啮齿动物模型系统相对于其它哺乳动物物种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和尚未解决的问题提供了基础，即在生理和病理生理条件下是否有机制触发分娩的发生。目前正在利用胚胎干细胞技术制造缺乏催产素受体的小鼠。