{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:22:35Z","timestamp":1790965355733,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:00:00Z","timestamp":1689552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Shanghai Zhangjiang National Independent Innovation Demonstration Zone Special Development Fund Major Project","award":["ZJ2022-ZD-006"],"award-info":[{"award-number":["ZJ2022-ZD-006"]}]},{"name":"Shanghai Biomedical Field Orientation Project","award":["22DX1900400"],"award-info":[{"award-number":["22DX1900400"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Multiple morphological abnormalities of the flagella, a severe form of asthenozoospermia, can lead to male infertility. Recent studies have implicated an association between human CFAP70 deficiency and multiple morphological abnormalities of the flagella; however, the underlying biological mechanism and supporting experimental evidence in animal models remain unclear. To address this gap, we used CRISPR\/Cas9 technology to generate Cfap70-deficient mice to investigate the relationship between Cfap70 deficiency and multiple morphological abnormalities of the flagella. Our findings show that the loss of CFAP70 leads to multiple morphological abnormalities of the flagella and spermiogenesis defects. Specifically, the lack of CFAP70 impairs sperm flagellum biogenesis and head shaping during spermiogenesis. Late-step spermatids from Cfap70-deficient mouse testis exhibited club-shaped sperm heads and abnormal disassembly of the manchette. Furthermore, we found that CFAP70 interacts with DNAI1 and DNAI2; Cfap70 deficiency also reduces the level of AKAP3 in sperm flagella, indicating that CFAP70 may participate in the flagellum assembly and transport of flagellar components. These findings provide compelling evidence implicating Cfap70 as a causative gene of multiple morphological abnormalities of the flagella and highlight the consequences of CFAP70 loss on flagellum biogenesis.<\/jats:p>","DOI":"10.1093\/biolre\/ioad076","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T19:59:46Z","timestamp":1689364786000},"page":"450-460","source":"Crossref","is-referenced-by-count":21,"title":["Experimental and molecular support for <i>Cfap70<\/i> as a causative gene of \u2018multiple morphological abnormalities of the flagella\u2019 with male infertility"],"prefix":"10.1093","volume":"109","author":[{"given":"Jingwen","family":"Chen","sequence":"first","affiliation":[{"name":"Shanghai Engineering Research Center of Reproductive Health Drug and Devices, School of Pharmacy NHC Key Laboratory of Reproduction Regulation, , , Shanghai , China"},{"name":"Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University NHC Key Laboratory of Reproduction Regulation, , , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaling","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Metabolism and Integrative Biology, Institute of Reproduction and Development, Obstetrics and Gynecology Hospital, Fudan University Shanghai Key Laboratory of Metabolic Remodeling and Health, , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangguo","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Reproductive Health Drug and Devices, School of Pharmacy NHC Key Laboratory of Reproduction Regulation, , , Shanghai , China"},{"name":"Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University NHC Key Laboratory of Reproduction Regulation, , , Shanghai , China"},{"name":"Institute of Metabolism and Integrative Biology, Institute of Reproduction and Development, Obstetrics and Gynecology Hospital, Fudan University Shanghai Key Laboratory of Metabolic Remodeling and Health, , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Reproductive Health Drug and Devices, School of Pharmacy NHC Key Laboratory of Reproduction Regulation, , , Shanghai , China"},{"name":"Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University NHC Key Laboratory of Reproduction Regulation, , , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingbo","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Metabolism and Integrative Biology, Institute of Reproduction and Development, Obstetrics and Gynecology Hospital, Fudan University Shanghai Key Laboratory of Metabolic Remodeling and Health, , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,7,17]]},"reference":[{"key":"2023101605090794100_ref1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1093\/humupd\/dmaa034","article-title":"Molecular genetics of infertility: loss-of-function mutations in humans and corresponding knockout\/mutated mice","volume":"27","author":"Jiao","year":"2021","journal-title":"Hum Reprod Update"},{"key":"2023101605090794100_ref2","doi-asserted-by":"crossref","DOI":"10.1016\/j.jgg.2023.05.008","article-title":"Homozygous nonsense variants of KCTD19 cause male infertility in humans and mice","author":"Zhang","year":"2023","journal-title":"J Genet Genomics"},{"key":"2023101605090794100_ref3","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male 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