The Hook1 gene is non-functional in the abnormal spermatozoon head shape (azh) mutant mouse

• Published in: Human molecular genetics 2002-07, Vol.11 (14), p.1647-1658
• Main Authors: Mendoza-Lujambio, Irene, Burfeind, Peter, Dixkens, Christa, Meinhardt, Andreas, Hoyer-Fender, Sigrid, Engel, Wolfgang, Neesen, Juergen
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Animals; Binding Sites; Biological and medical sciences; Chromosome Mapping; Classical genetics, quantitative genetics, hybrids; Cloning, Molecular; Dimerization; Exons; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genetics of eukaryotes. Biological and molecular evolution; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Microtubules - metabolism; Microtubules - ultrastructure; Molecular Sequence Data; Non tumoral diseases; Sequence Deletion; Sperm Head - metabolism; Sperm Head - pathology; Spermatozoa - metabolism; Spermatozoa - pathology; Spermatozoa - ultrastructure; Testis - metabolism; Testis - pathology; Vertebrata
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/11.14.1647

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.