UNIGE document Scientific Article
previous document  unige:109392  next document
add to browser collection
Title

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

Authors
Coutton, Charles
Published in Nature Communications. 2018, vol. 9, no. 1, p. 686
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 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.
Identifiers
PMID: 29449551
Full text
Article (Published version) (9.2 MB) - public document Free access
Structures
Research group Mécanismes moléculaires et génétiques du développement sexuel (778)
Citation
(ISO format)
COUTTON, Charles et al. Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human. In: Nature Communications, 2018, vol. 9, n° 1, p. 686. https://archive-ouverte.unige.ch/unige:109392

46 hits

21 downloads

Update

Deposited on : 2018-10-19

Export document
Format :
Citation style :