Back to Search
Start Over
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.
- 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.
- Subjects :
- Adult
Animals
Axoneme
Clustered Regularly Interspaced Short Palindromic Repeats
Cohort Studies
Cytoskeletal Proteins
Fertility
Flagella metabolism
Homozygote
Humans
Male
Mice
Mice, Knockout
Microscopy, Immunoelectron
Middle Aged
Sperm Motility
Spermatozoa metabolism
Exome Sequencing
Flagella physiology
Infertility, Male genetics
Microtubule Proteins genetics
Mutation
Nuclear Proteins genetics
Peptide Hydrolases genetics
Spermatozoa physiology
Trypanosoma physiology
Subjects
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