COUTTON, Charles; VARGAS, Alexandra S.; AMIRI-YEKTA, Amir; KHERRAF, Zine-Eddine; FOURATI BEN MUSTAPHA, Selima; LE TANNO, Pauline; WAMBERGUE LEGRAND, Clémentine; KARAOUZÈNE, Thomas; MARTINEZ, Guillaume; CROUZY, Serge; DANESHIPOUR, Abbas; HOSSEINI, Seyedeh Hanieh; MITCHELL, Valerie; HALOUANI, Lazhar; OUAFI, Marrakchi; MAKNI, Mounir; LATROUS, Habib; KHAROUF, Mahmoud; DELEUZE, Jean-François; BOLAND, Anne; HENNEBICQ, Sylviane; SATRE, Veronique; JOUK, Pierre-Simon; THIERRY-MIEG, Nicolas; CONNE, Béatrice; DACHEUX, Denis; LANDREIN, Nicolas; SCHMITT, Alain; STOUVENEL, Laurence; LORES, Patrick; EL KHOURI, Elma; BOTTARI, Serge P.; FAURE, Julien; WOLF, Jean Philippe; PERNET-GALLAY, Karine; ESCOFFIER, Jessica; GOURABI, Hamid; ROBINSON, Derrick R; NEF, Serge; DULIOUST, Emmanuel; ZOUARI, Raoudha; BONHIVERS, Melanie; TOURE, Aminata; ARNOULT, Christophe; RAY, Pierre F.

doi:10.1038/s41467-017-02792-7

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Article de revue

Ce document a été publié dans

Nature Communications. 2018-02-15, vol. 9, p. 686

Nature Publishing Group

Résumé en anglais

Spermatogenesis defects concern millions of men worldwide, yet the vast majority remains undiagnosed. Here we report men with primary infertility due to multiple morphological abnormalities of the sperm flagella with severe disorganization of the sperm axoneme, a microtubule-based structure highly conserved throughout evolution. Whole-exome sequencing was performed on 78 patients allowing the identification of 22 men with bi-allelic mutations in DNAH1 (n = 6), CFAP43 (n = 10), and CFAP44 (n = 6). CRISPR/Cas9 created homozygous CFAP43/44 male mice that were infertile and presented severe flagellar defects confirming the human genetic results. Immunoelectron and stimulated-emission-depletion microscopy performed on CFAP43 and CFAP44 orthologs in $Trypanosoma\ brucei$ evidenced that both proteins are located between the doublet microtubules 5 and 6 and the paraflagellar rod. Overall, we demonstrate that CFAP43 and CFAP44 have a similar structure with a unique axonemal localization and are necessary to produce functional flagella in species ranging from $Trypanosoma$ to human.< Réduire

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https://oskar-bordeaux.fr/handle/20.500.12278/182816

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http://dx.doi.org/10.1038/s41467-017-02792-7

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Développment d'une infrastructure française distribuée coordonnée
Génétique et Physiopathologie des anomalies morphologiques du flagelle spermatique associé à une infertilité masculine.
Anévrismes intracraniens : des formes familiales aux méchanismes physiopathologiques - ANR-15-CE17-0008

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MFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234

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Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in $Trypanosoma$ and human.

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