title: The Hook1 gene is non-functional in the abnormal spermatozoon head shape (azh) mutant mouse.
abstract: In mice carrying the autosomal recessive mutation 'abnormal spermatozoon head shape' (azh) all spermatozoa display a highly abnormal head morphology that differs drastically from the compact and hook-shaped head of the normal murine sperm. Moreover, the azh mutation causes tail abnormalities often resulting in coiled sperm tails or in the decapitation of the sperm head from the flagellum. We have isolated and characterized murine Hook1 cDNA and analyzed the corresponding genomic structure. Furthermore, the Hook1 gene was mapped to the same region on chromosome 4 to which the azh locus was previously linked. The Hook1 gene is predominantly expressed in haploid male germ cells, and immunohistochemical analysis revealed that Hook1 is responsible for the linkage of the microtubular manchette and the flagellum to cellular structures. Here, we report that the azh mutation is due to a deletion of exons 10 and 11 in the murine Hook1 gene leading to a non-functional protein. Our results indicate that loss of Hook1 function results in ectopic positioning of microtubular structures within the spermatid and causes the azh phenotype. Therefore, the human HOOK1 gene could serve as a candidate gene for male infertility due to teratozoospermia or decapitation defects.
authors.affiliation: Institute of Human Genetics, Department of Zoology and Developmental Biology, University of Göttingen, 37073 Göttingen, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Mendoza-Lujambio
authors.forename: Peter
authors.initials: P
authors.lastname: Burfeind
authors.forename: Christa
authors.initials: C
authors.lastname: Dixkens
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinhardt
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hoyer-Fender
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Engel
authors.forename: Juergen
authors.initials: J
authors.lastname: Neesen
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D019281:Dimerization; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008969:Molecular Sequence Data; D017384:Sequence Deletion; D013077:Sperm Head / Q000378:metabolism / Q000473:pathology*; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D013737:Testis / Q000378:metabolism* / Q000473:pathology
chemical_list: C471056:Hook1 protein, mouse; D008869:Microtubule-Associated Proteins; C471055:hook1 protein, human