title: Coiled-coil domain containing 42 (Ccdc42) is necessary for proper sperm development and male fertility in the mouse.
abstract: Spermiogenesis is the differentiation of spermatids into motile sperm consisting of a head and a tail. The head harbors a condensed elongated nucleus partially covered by the acrosome-acroplaxome complex. Defects in the acrosome-acroplaxome complex are associated with abnormalities in sperm head shaping. The head-tail coupling apparatus (HTCA), a complex structure consisting of two cylindrical microtubule-based centrioles and associated components, connects the tail or flagellum to the sperm head. Defects in the development of the HTCA cause sperm decapitation and disrupt sperm motility, two major contributors to male infertility. Here, we provide data indicating that mutations in the gene Coiled-coil domain containing 42 (Ccdc42) is associated with malformation of the mouse sperm flagella. In contrast to many other flagella and motile cilia genes, Ccdc42 expression is only observed in the brain and developing sperm. Male mice homozygous for a loss-of-function Ccdc42 allele (Ccdc42(KO)) display defects in the number and location of the HTCA, lack flagellated sperm, and are sterile. The testes enriched expression of Ccdc42 and lack of other phenotypes in mutant mice make it an ideal candidate for screening cases of azoospermia in humans.
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Pasek
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Malarkey
authors.affiliation: Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA.
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Berbari
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kesterson
authors.affiliation: Department of Cell Biology and Anatomy, The Sophie Davis School of Biomedical Education, The City University of New York, New York, NY, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Tres
authors.affiliation: Department of Cell Biology and Anatomy, The Sophie Davis School of Biomedical Education, The City University of New York, New York, NY, USA.
authors.forename: Abraham L
authors.initials: AL
authors.lastname: Kierszenbaum
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: byoder@uab.edu.
authors.forename: Bradley K
authors.initials: BK
authors.lastname: Yoder
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D005298:Fertility / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013077:Sperm Head / Q000378:metabolism* / Q000648:ultrastructure; D013081:Sperm Motility / Q000235:genetics; D013082:Sperm Tail / Q000378:metabolism* / Q000648:ultrastructure; D013087:Spermatids / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D013737:Testis / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D016808:Tetrahymena thermophila / Q000166:cytology / Q000235:genetics / Q000378:metabolism
chemical_list: C000610414:Ccdc42 protein, mouse; D011506:Proteins; D049452:Green Fluorescent Proteins
keywords: Ccdc42; Infertility; Intramanchette transport; Sperm; Sperm head–tail coupling apparatus