{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:47:07Z","timestamp":1791308827976,"version":"4.3.1"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,10,21]],"date-time":"2005-10-21T00:00:00Z","timestamp":1129852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Loss of <jats:italic>Nkx3.1<\/jats:italic> function in mice results in defects in prostate development and epithelial hyperplasia, indicating that this gene plays important roles in both the initiation and maintenance of prostate differentiation. In humans, decreased NKX3.1 expression is associated with the progression of prostate cancer. Despite these roles in prostate development and disease, the transcriptional regulation of <jats:italic>Nkx3.1<\/jats:italic> has not been systematically addressed. A reporter gene approach in transgenic mice was used to identify regulatory regions that dictate the expression pattern of <jats:italic>Nkx3.1<\/jats:italic>. A 32\u2010kb DNA fragment from the <jats:italic>Nkx3.1<\/jats:italic> locus that specifies the expected expression pattern during embryogenesis and postnatal life has been identified. Deletion analyses demonstrated that <jats:italic>cis<\/jats:italic>\u2010regulatory elements that mediate expression in distinct sites are separable. A 5\u2010kb fragment downstream of the <jats:italic>Nkx3.1<\/jats:italic> coding region contains elements that support expression in the prostate and bulbourethral glands, whereas an upstream fragment contains elements that direct expression in somites and testes. Reporter gene expression analyses also revealed several previously unknown sites of <jats:italic>Nkx3.1<\/jats:italic> expression in males, including urethral glands, glandular cells in the urethral diverticulum and basal epithelial cells in the prostate. In addition, these analyses revealed <jats:italic>Nkx3.1<\/jats:italic> expression in female urethral glands. The identification of <jats:italic>Nkx3.1 cis<\/jats:italic>\u2010regulatory elements provides a unique starting point to dissect signaling pathways involved in prostate organogenesis and pathogenesis and provides a system to perturb gene expression throughout prostate development. Developmental Dynamics 234:961\u2013973, 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.20596","type":"journal-article","created":{"date-parts":[[2005,10,21]],"date-time":"2005-10-21T17:46:30Z","timestamp":1129916790000},"page":"961-973","source":"Crossref","is-referenced-by-count":25,"title":["Distinct regulatory elements mediate the dynamic expression pattern of <i>Nkx3.1<\/i>"],"prefix":"10.1002","volume":"234","author":[{"given":"Hui","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura N.","family":"Mutton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail S.","family":"Prins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J.","family":"Bieberich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,10,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.819500"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.5.1495-1503.2002"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.9.5.2254"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.7b.1325"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.8.966"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.21.8462"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.50.31779"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/23.23.4850"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.6.2426"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/19315"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.11.6379"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1210\/mend.11.9.9974","article-title":"A 6\u2010kb promoter fragment mimics in transgenic mice the prostate\u2010 specific and androgen\u2010regulated expression of the endogenous prostate\u2010 specific antigen gene in humans","volume":"11","author":"Cleutjens KB","year":"1997","journal-title":"Mol Endocrinol"},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1210\/mend.11.2.9883","article-title":"An androgen response element in a far upstream enhancer region is essential for high, androgen\u2010regulated activity of the prostate\u2010 specific antigen promoter","volume":"11","author":"Cleutjens KB","year":"1997","journal-title":"Mol Endocrinol"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.2990110304"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.2990100208"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/322383a0"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(83)01031-9"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.8.2.230"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90584-8"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1997.4715"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.20.7716"},{"key":"e_1_2_6_23_1","first-page":"2999","article-title":"Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis","volume":"62","author":"Kim MJ","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.1.60"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(97)00168-8"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.17.9695"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.13.1654"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00076a020"},{"key":"e_1_2_6_29_1","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1242\/dev.126.10.2215","article-title":"Targeted disruption of the homeobox transcription factor Nkx2\u20133 in mice results in postnatal lethality and abnormal development of small intestine and spleen","volume":"126","author":"Pabst O","year":"1999","journal-title":"Development"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1.3.268"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend-5-12-1921"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(99)80397-2"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(00)00355-5"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.12.7043"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.19.4187"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199705)209:1<127::AID-AJA12>3.0.CO;2-Z"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.10397"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.1993.1021"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.12.2213"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.6.1269"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(99)00084-2"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0177(2000)9999:9999<::AID-DVDY1054>3.0.CO;2-E"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.24.5699"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.12.026"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6446"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0045(19970701)32:2<129::AID-PROS8>3.0.CO;2-H"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.7a.1277"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.24.4971"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8386"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(00)00037-3"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1170361"}],"container-title":["Developmental Dynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fdvdy.20596","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvdy.20596","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:33:08Z","timestamp":1760401988000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/dvdy.20596"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,10,21]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2005,12]]}},"alternative-id":["10.1002\/dvdy.20596"],"URL":"https:\/\/doi.org\/10.1002\/dvdy.20596","archive":["Portico"],"relation":{},"ISSN":["1058-8388","1097-0177"],"issn-type":[{"value":"1058-8388","type":"print"},{"value":"1097-0177","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,10,21]]}}}