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

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

Authors :
Coutton C
Vargas AS
Amiri-Yekta A
Kherraf ZE
Ben Mustapha SF
Le Tanno P
Wambergue-Legrand C
Karaouzène T
Martinez G
Crouzy S
Daneshipour A
Hosseini SH
Mitchell V
Halouani L
Marrakchi O
Makni M
Latrous H
Kharouf M
Deleuze JF
Boland A
Hennebicq S
Satre V
Jouk PS
Thierry-Mieg N
Conne B
Dacheux D
Landrein N
Schmitt A
Stouvenel L
Lorès P
El Khouri E
Bottari SP
Fauré J
Wolf JP
Pernet-Gallay K
Escoffier J
Gourabi H
Robinson DR
Nef S
Dulioust E
Zouari R
Bonhivers M
Touré A
Arnoult C
Ray PF
Source :
Nature communications [Nat Commun] 2018 Feb 15; Vol. 9 (1), pp. 686. Date of Electronic Publication: 2018 Feb 15.
Publication Year :
2018

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.

Details

Language :
English
ISSN :
2041-1723
Volume :
9
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
29449551
Full Text :
https://doi.org/10.1038/s41467-017-02792-7