{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T08:39:02Z","timestamp":1789893542662,"version":"4.0.1"},"reference-count":53,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,7,13]],"date-time":"2012-07-13T00:00:00Z","timestamp":1342137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:p>\n                    The androgen receptor (AR) recognizes two types of DNA elements that are dimers of 5\u2032\u2010AGAACA\u20103\u2032\u2010like hexamers, either organized as inverted or direct repeats. We developed a mouse model [(specificity affecting AR knock\u2010in (SPARKI)] in which the AR DNA\u2010binding domain was mutated such that it lost binding to direct repeats but not to inverted elements. The impaired fertility of the male SPARKI mice correlates with the reduced motility of the spermatozoa, a characteristic that is developed during transit through the epididymis. Comparative transcriptome analyses revealed that the expression of 39 genes is changed in SPARKI epididymis. Remarkably, the expression of the steroid 5\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010reductase type II (Srd5\n                    <jats:italic>\u03b1<\/jats:italic>\n                    2) gene, which metabolizes testosterone into the more potent dihydrotestosterone, is reduced 4\u2010fold in SPARKI\n                    <jats:italic>vs.<\/jats:italic>\n                    wild type. The comparison of the SPARKI phenotype with that of\n                    <jats:italic>Srd5\u03b12<\/jats:italic>\n                    \u2010knockout mice shows, however, that the reduced Srd5\n                    <jats:italic>\u03b1<\/jats:italic>\n                    2 expression cannot explain all defects of the SPARKI epididymis. Moreover, we describe three new selective androgen response elements (AREs), which control the androgen responsiveness of the\n                    <jats:italic>Srd5\u03b12<\/jats:italic>\n                    gene. We conclude that the SPARKI model can be considered a knockout model for AR functioning\n                    <jats:italic>via<\/jats:italic>\n                    selective AREs and that this has a dramatic effect on sperm maturation in the epididymis.\u2014Kerkhofs, S., Dubois, V., De Gendt, K., Helsen, C., Clinckemalie, L., Spans, L., Schuit, F., Boonen, S., Vanderschueren, D., Saunders, P. T. K., Verhoeven, G., Claessens, F. A role for selective androgen response elements in the development of the epididymis and the androgen control of the 5\n                    <jats:italic>\u03b1<\/jats:italic>\n                    reductase II gene.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 4360\u20134372 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-202283","type":"journal-article","created":{"date-parts":[[2012,7,14]],"date-time":"2012-07-14T05:53:42Z","timestamp":1342245222000},"page":"4360-4372","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["A role for selective androgen response elements in the development of the epididymis and the androgen control of the 5\n                    <i>\u03b1<\/i>\n                    reductase II gene"],"prefix":"10.1096","volume":"26","author":[{"given":"Stefanie","family":"Kerkhofs","sequence":"first","affiliation":[{"name":"Molecular Endocrinology Laboratory Katholieke Universiteit Leuven Campus Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Dubois","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology Laboratory Katholieke Universiteit Leuven Campus Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"De Gendt","sequence":"additional","affiliation":[{"name":"Division of Clinical and Experimental Endocrinology Katholieke Universiteit Leuven Campus Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Helsen","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology Laboratory Katholieke Universiteit Leuven Campus Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesbeth","family":"Clinckemalie","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology Laboratory Katholieke Universiteit Leuven Campus Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lien","family":"Spans","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology Laboratory Katholieke Universiteit Leuven Campus Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans","family":"Schuit","sequence":"additional","affiliation":[{"name":"Gene Expression Unit, Department of Cellular and Molecular Medicine Katholieke Universiteit Leuven Campus Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Boonen","sequence":"additional","affiliation":[{"name":"Division of Clinical and Experimental Endocrinology Katholieke Universiteit Leuven Campus Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Vanderschueren","sequence":"additional","affiliation":[{"name":"Division of Clinical and Experimental Endocrinology Katholieke Universiteit Leuven Campus Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa T. K.","family":"Saunders","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Reproductive Sciences Unit The Queen's Medical Research Institute Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Verhoeven","sequence":"additional","affiliation":[{"name":"Division of Clinical and Experimental Endocrinology Katholieke Universiteit Leuven Campus Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Claessens","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology Laboratory Katholieke Universiteit Leuven Campus Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,7,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.843800"},{"key":"e_1_2_7_3_1","first-page":"577","article-title":"Steroid 5\u03b1\u2010reductase 2 deficiency","volume":"14","author":"Wilson J. D.","year":"1993","journal-title":"Endocr. Rev."},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00247"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","DOI":"10.1621\/nrs.06008","article-title":"Diverse roles of androgen receptor (AR) domains in AR\u2010mediated signaling","volume":"6","author":"Claessens F.","year":"2008","journal-title":"Nucl. Recept. Signal."},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"R11","DOI":"10.1016\/0303-7207(93)90160-L","article-title":"Interaction of androgen and glucocorticoid receptor DNA\u2010binding domains with their response elements","volume":"90","author":"De Vos P.","year":"1993","journal-title":"Mol. Cell. Endocrinol."},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.24.11660"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.7.1.23"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3410515"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20020912"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-010-0302-1"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2009-0310"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610814104"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7262.2007.00285.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1530\/rep.0.1250871"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4615-0679-9_5","volume-title":"Epididymal Cell Types and Their Functions","author":"Hermo L.","year":"2002"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.142.11.4652"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.5.7472"},{"key":"e_1_2_7_19_1","volume-title":"WHO Laboratory Manual for the Examination and Processing of Human Semen","author":"World Health Organization","year":"2010"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.050811"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205928200"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.37.24216"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.103.021493"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.106.057323"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gam051"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.103.026302"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod52.6.1350"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06862"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod65.3.696"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.105.039719"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1053\/beem.2001.0120"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0226"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.16.12298"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.07.025"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1071\/RD9950731"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2605.1999.00151.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1995.tb00532.x"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308114100"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.212474399"},{"key":"e_1_2_7_40_1","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4615-0679-9_17","volume-title":"Androgenic Regulation of the Structure and Functions of the Epididymis","author":"Ezer N.","year":"2002"},{"key":"e_1_2_7_41_1","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1210\/en.2010-0768","article-title":"Targeted inactivation of the androgen receptor gene in murine proximal epididymis causes epithelial hypotrophy and obstructive azoospermia","volume":"152","author":"Krutskikh A.","journal-title":"Endocrinology"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1999.tb02555.x"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.109.079053"},{"key":"e_1_2_7_44_1","doi-asserted-by":"crossref","first-page":"e15061","DOI":"10.1371\/journal.pone.0015061","article-title":"Role of carbonic anhydrase IV in the bicarbonate\u2010mediated activation of murine and human sperm","volume":"5","author":"Wandernoth P. M.","journal-title":"PLoS One"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:HIJO.0000023387.02793.af"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.104.038448"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod63.2.612"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2006.01.004"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.149.3.707"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.05.081"},{"key":"e_1_2_7_51_1","first-page":"163","article-title":"Different binding of testosterone, 19\u2010nortestosterone and their 5\u03b1\u2010reduced derivatives to the androgen receptor of the rat seminal vesicle: a step toward the understanding of the anabolic action of nortestosterone","volume":"80","author":"Toth M.","year":"1982","journal-title":"Endokrinologie"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1564207"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7401046"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.05.041"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.11-202283","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.11-202283","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.11-202283","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T21:32:24Z","timestamp":1761687144000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.11-202283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,13]]},"references-count":53,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1096\/fj.11-202283"],"URL":"https:\/\/doi.org\/10.1096\/fj.11-202283","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,13]]},"assertion":[{"value":"2012-03-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-07-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}