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Within this locus, we identified a new candidate gene that could be implicated in a reproductive phenotype:<jats:italic>Tex44<\/jats:italic>(<jats:italic>Testis-expressed protein 44<\/jats:italic>). We thus performed a CRISPR\/Cas9-mediated complete deletion of this gene in mice in order to study its function.<jats:italic>Tex44<\/jats:italic>-KO males were severely hypofertile in vivo and in vitro due to a drastic reduction of sperm motility which itself resulted from important morphological sperm abnormalities. Namely,<jats:italic>Tex44<\/jats:italic>-KO sperm showed a disorganized junction between the midpiece and the principal piece of the flagellum, leading to a 180\u00b0 flagellar bending in this region. In addition, the loss of some axonemal microtubule doublets and outer dense fibers in the flagellum\u2019s principal piece has been observed. Our results suggest that, in mice, TEX44 is implicated in the correct set-up of the sperm flagellum during spermiogenesis and its absence leads to flagellar abnormalities and consequently to severe male hypofertility.<\/jats:p><jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1186\/s11658-024-00587-5","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T06:01:47Z","timestamp":1715752907000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The lack of Tex44 causes severe subfertility with flagellar abnormalities in male mice"],"prefix":"10.1186","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2932-9755","authenticated-orcid":false,"given":"Sophie","family":"Dupuis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3175-3870","authenticated-orcid":false,"given":"Marie-Sophie","family":"Girault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Le Beulze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5260-5343","authenticated-orcid":false,"given":"C\u00f4me","family":"Ialy-Radio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Berm\u00fadez-Guzm\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9724-3831","authenticated-orcid":false,"given":"Ahmed","family":"Ziyyat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8204-1855","authenticated-orcid":false,"given":"Sandrine","family":"Barbaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"587_CR1","unstructured":"WHO TEAM\u202f: sexual and reproductive health and research. 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Ziyyat (2018\u20132023). Local (C2EA-34, Comit\u00e9 d\u2019\u00e9thique en mati\u00e8re d\u2019exp\u00e9rimentation animale Paris Descartes) and governmental (Apafis) Ethics Committees act on the Basel Declaration.Human samples were obtained after informed consents of the patients. The GERMETHEQUE pilotage committee approved the design of this study under the number 20220101. The Biobank has a declaration DC-2021-4820 and an authorization AC-2019-3487 at the national level. These Ethics Committees act on the Helsinki Declaration.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors have no financial interests to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"74"}}