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In most cases the PR is induced by estrogen, implying that many of the in vivo effects attributed to progesterone could also be the result of concomitantly administered estrogen. Therefore, to clearly define those physiological events that are specifically attributable to progesterone in vivo, we have generated a mouse model carrying a null mutation of the PR gene using embryonic stem cell\/gene targeting techniques. Male and female embryos homozygous for the PR mutation developed normally to adulthood. However, the adult female PR mutant displayed significant defects in all reproductive tissues. These included an inability to ovulate, uterine hyperplasia and inflammation, severely limited mammary gland development, and an inability to exhibit sexual behavior. Collectively, these results provide direct support for progesterone's role as a pleiotropic coordinator of diverse reproductive events that together ensure species survival.<\/jats:p>","DOI":"10.1101\/gad.9.18.2266","type":"journal-article","created":{"date-parts":[[2007,6,5]],"date-time":"2007-06-05T17:15:46Z","timestamp":1181063746000},"page":"2266-2278","source":"Crossref","is-referenced-by-count":1534,"title":["Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities."],"prefix":"10.1101","volume":"9","author":[{"given":"J P","family":"Lydon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F J","family":"DeMayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C R","family":"Funk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S K","family":"Mani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A R","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C A","family":"Montgomery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Shyamala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O M","family":"Conneely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B W","family":"O'Malley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[1995,9,15]]},"reference":[{"key":"2021111418251720000_9.18.2266.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2781282"},{"key":"2021111418251720000_9.18.2266.2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"2021111418251720000_9.18.2266.3","first-page":"51","article-title":"Topography of DNA synthesis in the mammary gland of the C3H mouse and its control by ovarian hormones: An autoradiographic study.","volume":"1","year":"1968","journal-title":"Cell Tissue Kinetics"},{"key":"2021111418251720000_9.18.2266.4","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(89)90060-5"},{"key":"2021111418251720000_9.18.2266.5","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-11-2-201"},{"key":"2021111418251720000_9.18.2266.6","doi-asserted-by":"publisher","DOI":"10.1210\/en.135.1.307"},{"key":"2021111418251720000_9.18.2266.7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.77.3.873"},{"key":"2021111418251720000_9.18.2266.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.7.1991"},{"key":"2021111418251720000_9.18.2266.9","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-11-2-266"},{"key":"2021111418251720000_9.18.2266.10","doi-asserted-by":"publisher","DOI":"10.1038\/icb.1990.53"},{"key":"2021111418251720000_9.18.2266.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.2426779"},{"key":"2021111418251720000_9.18.2266.12","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(87)90395-0"},{"key":"2021111418251720000_9.18.2266.13","first-page":"6052","article-title":"Direct action of 17-beta estradiol on mouse mammary ducts analyzed by sustained release implants and steroid autoradiography.","volume":"47","year":"1987","journal-title":"Cancer Res."},{"key":"2021111418251720000_9.18.2266.14","doi-asserted-by":"crossref","first-page":"4207","DOI":"10.1016\/S0021-9258(19)84984-0","article-title":"Mutational analysis of the chicken progesterone receptor.","volume":"264","year":"1989","journal-title":"J. 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