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As spermatozoa from the proximal caudal epididymis can fertilize eggs, proteins from the caput and corpus epididymis are required for sperm maturation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Microarray analysis identified that more than 17,000 genes are expressed in the epididymis; however, few of these genes demonstrate expression restricted to the epididymis. To analyze epididymis\u2010enriched gene function in\u00a0vivo, we generated knockout (<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) mutations in nine genes that are abundantly expressed in the caput and corpus region of the epididymis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice were generated using the <jats:styled-content style=\"fixed-case\">CRISPR<\/jats:styled-content>\/Cas9 system. The histology of the epididymis was observed with hematoxylin and eosin staining. <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> males were caged with wild\u2010type females for 3\u20136\u00a0months to check fertility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We generated individual mutant mouse lines having indel mutations in <jats:italic>Pate1<\/jats:italic>,<jats:italic> Pate2<\/jats:italic>, or <jats:italic>Pate3<\/jats:italic>. We also deleted the coding regions of <jats:italic>Clpsl2, Epp13<\/jats:italic>, and <jats:italic>Rnase13<\/jats:italic>, independently. Finally, the 150\u00a0kb region encoding <jats:italic>Gm1110<\/jats:italic>,<jats:italic> Glb1l2<\/jats:italic>, and <jats:italic>Glb1l3<\/jats:italic> was deleted to generate a triple <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mouse line. Histology of the epididymis and sperm morphology of all <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> lines were comparable to control males. The females mated with these <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> males delivered pups at comparable numbers as control males.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and conclusion<\/jats:title><jats:p>We revealed that nine genes abundantly expressed in the caput and corpus epididymis are dispensable for sperm function and male fecundity. <jats:styled-content style=\"fixed-case\">CRISPR<\/jats:styled-content>\/Cas9\u2010mediated <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice generation accelerates the screening of epididymis\u2010enriched genes for potential functions in reproduction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12621","type":"journal-article","created":{"date-parts":[[2019,3,30]],"date-time":"2019-03-30T06:55:50Z","timestamp":1553928950000},"page":"644-653","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Nine genes abundantly expressed in the epididymis are not essential for male fecundity in mice"],"prefix":"10.1111","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0260-7861","authenticated-orcid":false,"given":"T.","family":"Noda","sequence":"first","affiliation":[{"name":"Research Institute for Microbial Diseases Osaka University Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases Osaka University Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Nozawa","sequence":"additional","affiliation":[{"name":"Center for Drug Discovery Baylor College of Medicine Houston TX USA"},{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Osaka University Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. J.","family":"Devlin","sequence":"additional","affiliation":[{"name":"Center for Drug Discovery Baylor College of Medicine Houston TX USA"},{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine Houston TX USA"},{"name":"Interdepartmental Program in Translational Biology &amp; Molecular Medicine Baylor College of Medicine Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. M.","family":"Matzuk","sequence":"additional","affiliation":[{"name":"Center for Drug Discovery Baylor College of Medicine Houston TX USA"},{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine Houston TX USA"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston TX USA"},{"name":"Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX USA"},{"name":"Department of Pharmacology and Chemical Biology Baylor College of Medicine Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9859-6217","authenticated-orcid":false,"given":"M.","family":"Ikawa","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases Osaka University Suita Osaka Japan"},{"name":"Graduate School of Pharmaceutical Sciences Osaka University Suita Osaka Japan"},{"name":"Institute of Medical Science The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2004.10.008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231143"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.105.039719"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-205211"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801454200"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2015.04.024"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev003"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26668"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep03355"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/dgd.12113"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1608458113"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7128-2_6"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioy247"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0008"},{"key":"e_1_2_9_16_1","first-page":"999","volume-title":"The Physiology of Reproduction","author":"Robaire B","year":"1988"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012515400-0\/50027-0"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.04.025"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.113.116863"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.08.022"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2016.08.007"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.071589"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fandr.12621","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.12621","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/andr.12621","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.12621","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T07:19:52Z","timestamp":1694330392000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.12621"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,29]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1111\/andr.12621"],"URL":"https:\/\/doi.org\/10.1111\/andr.12621","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,29]]},"assertion":[{"value":"2018-11-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}