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Despite many studies, the molecular details of the globozoospermia etiology are still poorly understood. Serine-rich single-pass membrane protein 1 (Ssmem1) is a conserved testis-specific gene in mammals. In this study, we generated Ssmem1 knockout (KO) mice using the CRISPR\/Cas9 system, demonstrated that Ssmem1 is essential for male fertility in mice, and found that SSMEM1 protein is expressed during spermatogenesis but not in mature sperm. The sterility of the Ssmem1 KO (null) mice is associated with globozoospermia and loss of sperm motility. To decipher the mechanism causing the phenotype, we analyzed testes with transmission electron microscopy and discovered that Ssmem1-disrupted spermatids have abnormal localization of Golgi at steps eight and nine of spermatid development. Immunofluorescence analysis with anti-Golgin-97 to label the trans-Golgi network, also showed delayed movement of the Golgi to the spermatid posterior region, which causes failure of sperm head shaping, disorganization of the cell organelles, and entrapped tails in the cytoplasmic droplet. In summary, SSMEM1 is crucial for intracellular Golgi movement to ensure proper spatiotemporal formation of the sperm head that is required for fertilization. These studies and the pathway in which SSMEM1 functions have implications for human male infertility and identifying potential targets for nonhormonal contraception.<\/jats:p>","DOI":"10.1093\/biolre\/ioaa040","type":"journal-article","created":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T13:26:51Z","timestamp":1587130011000},"page":"244-253","source":"Crossref","is-referenced-by-count":16,"title":["Knockout of serine-rich single-pass membrane protein 1 (Ssmem1) causes globozoospermia and sterility in male mice\u2020"],"prefix":"10.1093","volume":"103","author":[{"given":"Kaori","family":"Nozawa","sequence":"first","affiliation":[{"name":"Center for Drug Discovery, Baylor College of Medicine, Houston, TX"},{"name":"Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","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":"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":"Darius J","family":"Devlin","sequence":"additional","affiliation":[{"name":"Center for Drug Discovery, Baylor College of Medicine, Houston, TX"},{"name":"Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX"},{"name":"Interdepartmental Program in Translational Biology & Molecular Medicine, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifeng","family":"Yu","sequence":"additional","affiliation":[{"name":"Center for Drug Discovery, Baylor College of Medicine, Houston, TX"},{"name":"Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiya","family":"Oura","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":"Takayuki","family":"Koyano","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics, Shigei Medical Research Institute, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics, Shigei Medical Research Institute, Okayama, Japan"}],"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, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin M","family":"Matzuk","sequence":"additional","affiliation":[{"name":"Center for Drug Discovery, Baylor College of Medicine, Houston, TX"},{"name":"Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,17]]},"reference":[{"key":"2020080406503359600_ref1","first-page":"347","article-title":"Tissue-based map of the human proteome","volume":"80","author":"Uhl\u00e9n","year":"2015","journal-title":"Science"},{"key":"2020080406503359600_ref2","doi-asserted-by":"crossref","first-page":"12201","DOI":"10.1073\/pnas.1635054100","article-title":"A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets","volume":"100","author":"Schultz","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2020080406503359600_ref3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11825-018-0181-7","article-title":"Spermatogenesest\u00f6rungen: Perspektiven f\u00fcr erweiterte genetische Diagnostik nach 20 Jahren unver\u00e4nderter 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