Cfap97d1 is important for flagellar axoneme maintenance and male mouse fertility

Autoři: Seiya Oura aff001;  Samina Kazi aff002;  Audrey Savolainen aff002;  Kaori Nozawa aff003;  Julio Castañeda aff001;  Zhifeng Yu aff003;  Haruhiko Miyata aff001;  Ryan M. Matzuk aff003;  Jan N. Hansen aff005;  Dagmar Wachten aff005;  Martin M. Matzuk aff003;  Renata Prunskaite-Hyyryläinen aff002
Působiště autorů: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan aff001;  Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland aff002;  Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, United States of America aff003;  Center for Drug Discovery, Baylor College of Medicine, Houston, Texas, United States of America aff004;  Institute of Innate Immunity, Biophysical Imaging, Medical Faculty, University of Bonn, Bonn, Germany aff005
Vyšlo v časopise: Cfap97d1 is important for flagellar axoneme maintenance and male mouse fertility. PLoS Genet 16(8): e32767. doi:10.1371/journal.pgen.1008954
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008954


The flagellum is essential for sperm motility and fertilization in vivo. The axoneme is the main component of the flagella, extending through its entire length. An axoneme is comprised of two central microtubules surrounded by nine doublets, the nexin-dynein regulatory complex, radial spokes, and dynein arms. Failure to properly assemble components of the axoneme in a sperm flagellum, leads to fertility alterations. To understand this process in detail, we have defined the function of an uncharacterized gene, Cfap97 domain containing 1 (Cfap97d1). This gene is evolutionarily conserved in mammals and multiple other species, including Chlamydomonas. We have used two independently generated Cfap97d1 knockout mouse models to study the gene function in vivo. Cfap97d1 is exclusively expressed in testes starting from post-natal day 20 and continuing throughout adulthood. Deletion of the Cfap97d1 gene in both mouse models leads to sperm motility defects (asthenozoospermia) and male subfertility. In vitro fertilization (IVF) of cumulus-intact oocytes with Cfap97d1 deficient sperm yielded few embryos whereas IVF with zona pellucida-free oocytes resulted in embryo numbers comparable to that of the control. Knockout spermatozoa showed abnormal motility characterized by frequent stalling in the anti-hook position. Uniquely, Cfap97d1 loss caused a phenotype associated with axonemal doublet heterogeneity linked with frequent loss of the fourth doublet in the sperm stored in the epididymis. This study demonstrates that Cfap97d1 is required for sperm flagellum ultra-structure maintenance, thereby playing a critical role in sperm function and male fertility in mice.

Klíčová slova:

Flagella – Flagellar motility – Genetically modified animals – Heterozygosity – Microtubules – Mouse models – Sperm – Testes


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