Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in $Trypanosoma$ and human.
Language
en
Article de revue
This item was published in
Nature Communications. 2018-02-15, vol. 9, p. 686
Nature Publishing Group
English Abstract
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 ...Read more >
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.Read less <
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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
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