title: Rat hd mutation reveals an essential role of centrobin in spermatid head shaping and assembly of the head-tail coupling apparatus.
abstract: The hypodactylous (hd) locus impairs limb development and spermatogenesis, leading to male infertility in rats. We show that the hd mutation is caused by an insertion of an endogenous retrovirus into intron 10 of the Cntrob gene. The retroviral insertion in hd mutant rats disrupts the normal splicing of Cntrob transcripts and results in the expression of a truncated protein. During the final phase of spermiogenesis, centrobin localizes to the manchette, centrosome, and the marginal ring of the spermatid acroplaxome, where it interacts with keratin 5-containing intermediate filaments. Mutant spermatids show a defective acroplaxome marginal ring and separation of the centrosome from its normal attachment site of the nucleus. This separation correlates with a disruption of head-tail coupling apparatus, leading to spermatid decapitation during the final step of spermiogenesis and the absence of sperm in the epididymis. Cntrob may represent a novel candidate gene for presently unexplained hereditary forms of teratozoospermia and the "easily decapitated sperm syndrome" in humans.
authors.affiliation: Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague, Praha, Czech Republic. frantisek.liska@lf1.cuni.cz
authors.forename: Frantisek
authors.initials: F
authors.lastname: Liska
authors.forename: Claudia
authors.initials: C
authors.lastname: Gosele
authors.forename: Eugene
authors.initials: E
authors.lastname: Rivkin
authors.forename: Laura
authors.initials: L
authors.lastname: Tres
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Cardoso
authors.forename: Petra
authors.initials: P
authors.lastname: Domaing
authors.forename: Eliska
authors.initials: E
authors.lastname: Krejcí
authors.forename: Pavel
authors.initials: P
authors.lastname: Snajdr
authors.forename: Min Ae
authors.initials: MA
authors.lastname: Lee-Kirsch
authors.forename: Dirk G
authors.initials: DG
authors.lastname: de Rooij
authors.forename: Dirk G de
authors.initials: DG
authors.lastname: Rooij
authors.forename: Vladimír
authors.initials: V
authors.lastname: Kren
authors.forename: Drahomíra
authors.initials: D
authors.lastname: Krenová
authors.forename: Abraham L
authors.initials: AL
authors.lastname: Kierszenbaum
authors.forename: Norbert
authors.initials: N
authors.lastname: Hubner
mesh_terms: D000818:Animals; D026481:Blotting, Far-Western; D018797:Cell Cycle Proteins / Q000502:physiology*; D018385:Centrosome / Q000378:metabolism; D020077:Endogenous Retroviruses / Q000235:genetics; D004822:Epididymis / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005801:Genes, Homeobox / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D007438:Introns / Q000235:genetics; D053555:Keratin-5 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013077:Sperm Head / Q000378:metabolism*; D013082:Sperm Tail / Q000378:metabolism*; D013087:Spermatids / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C583842:Cntrob protein, rat; D018398:Homeodomain Proteins; D053555:Keratin-5