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Many genes are shown to be essential for male fertility using knockout (KO) mice; however, there still remain genes to be analyzed to elucidate their molecular mechanism and their roles in spermatogenesis. Calcium- and integrin-binding protein 1 (CIB1) is a ubiquitously expressed protein that possesses three paralogs: CIB2, CIB3, and CIB4. It is reported that Cib1 KO male mice are sterile due to impaired haploid differentiation. In this study, we discovered that Cib4 is expressed strongly in mouse and human testis and begins expression during the haploid phase of spermatogenesis in mice. To analyze the function of CIB4 in vivo, we generated Cib4 KO mice using the CRISPR\/Cas9 system. Cib4 KO male mice are sterile due to impaired haploid differentiation, phenocopying Cib1 KO male mice. Spermatogenic cells isolated from seminiferous tubules demonstrate an essential function of CIB4 in the formation of the apical region of the sperm head. Further analysis of CIB4 function may shed light on the etiology of male infertility caused by spermatogenesis defects, and CIB4 could be a target for male contraceptives because of its dominant expression in the testis.<\/jats:p>","DOI":"10.1093\/biolre\/ioaa059","type":"journal-article","created":{"date-parts":[[2020,4,25]],"date-time":"2020-04-25T01:15:50Z","timestamp":1587777350000},"page":"235-243","source":"Crossref","is-referenced-by-count":13,"title":["CIB4 is essential for the haploid phase of spermatogenesis in mice\u2020"],"prefix":"10.1093","volume":"103","author":[{"given":"Zoulan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan"},{"name":"Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiko","family":"Miyata","sequence":"additional","affiliation":[{"name":"Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kaneda","sequence":"additional","affiliation":[{"name":"Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan"},{"name":"Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio M","family":"Castaneda","sequence":"additional","affiliation":[{"name":"Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akane","family":"Morohoshi","sequence":"additional","affiliation":[{"name":"Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan"},{"name":"Graduate School of Medicine, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifeng","family":"Yu","sequence":"additional","affiliation":[{"name":"Center for Drug Discovery, Baylor College of Medicine, Houston, TX, USA"},{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin M","family":"Matzuk","sequence":"additional","affiliation":[{"name":"Center for Drug Discovery, Baylor College of Medicine, Houston, TX, USA"},{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahito","family":"Ikawa","sequence":"additional","affiliation":[{"name":"Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan"},{"name":"Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan"},{"name":"Graduate School of Medicine, Osaka University, Suita, Osaka, Japan"},{"name":"The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,25]]},"reference":[{"key":"2020080407010275400_ref1","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrg911","article-title":"Mouse models of male infertility","volume":"3","author":"Cooke","year":"2002","journal-title":"Nat Rev Genet"},{"key":"2020080407010275400_ref2","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.fertnstert.2012.11.037","article-title":"Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach","volume":"99","author":"Thoma","year":"2013","journal-title":"Fertil Steril"},{"key":"2020080407010275400_ref3","doi-asserted-by":"crossref","first-page":"42","DOI":"10.2174\/1874255601103010042","article-title":"Genetic testing in male infertility","volume":"3","author":"Dada","year":"2011","journal-title":"Open Reprod Sci 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