Disease relevance of Hook1

• Moreover, the azh mutation causes tail abnormalities often resulting in coiled sperm tails or in the decapitation of the sperm head from the flagellum [1].
• The strain B514, an M serotype 50 strain, is capable of causing a natural upper respiratory infection leading to death in mice, as reported by Hook et al. in 1960 (E. W. Hook, R. R. Wagner, and R. C. Lancefield, Am. J. Hyg. 72:111-119, 1960) [2].
• Tripterygium wilfordii Hook f. is a medicinal plant which possesses anti-fertility activity in males and has been used in China for the treatment of rheumatoid arthritis, chronic nephritis and other pulmonary diseases for years [3].
• Dihydroagarofuran sesquiterpenes, which were isolated from Tripterygium wilfordii Hook fil. var. regelii Makino and Euonymus sieboldianus Blume, showed inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) [4].
• The anticancer activity of dichloromethane extract of guduchi [Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms. Family: Menispermaceae (TCE)] in the mice transplanted with Ehrlich ascites carcinoma (EAC) was investigated [5].

High impact information on Hook1

• Our results indicate that loss of Hook1 function results in ectopic positioning of microtubular structures within the spermatid and causes the azh phenotype [1].
• Furthermore, the Hook1 gene was mapped to the same region on chromosome 4 to which the azh locus was previously linked [1].
• 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 [1].
• 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 [1].
• 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 [1].

Chemical compound and disease context of Hook1

• Therapeutic impact of the ethyl acetate extract of Tripterygium wilfordii Hook F on nephritis in NZB/W F1 mice [6].

Biological context of Hook1

• The azh locus was mapped by crossing mice with the mutation on a relatively pure C57BL/6J(B6) background with C3H/HeKam and backcrossing the F1 mice to B6-azh/azh mice [7].
• Results of this study indicate that the azh/azh mutant and offspring generated by intracytoplasmic sperm injection provide a valuable model for determining the role of the manchette and keratin-containing outer dense fibers and fibrous sheath during spermiogenesis [8].
• Male mice homozygous for the azh mutation produce spermatozoa with abnormal head shapes and have significantly reduced fecundity, to between 5% and 10% that of wild-type or heterozygous mice [9].
• We speculate that spermatid and sperm tail abnormalities in the azh/azh mutant could reflect structural and/or assembly deficiencies of peri-axonemal proteins responsible for maintaining a stiffened tail during spermiogenesis and sperm maturation [10].
• Triptolide, a novel diterpenoid triepoxide from Tripterygium wilfordii Hook. f., suppresses the production and gene expression of pro-matrix metalloproteinases 1 and 3 and augments those of tissue inhibitors of metalloproteinases 1 and 2 in human synovial fibroblasts [11].

Anatomical context of Hook1

• Studies on the Drosophila homolog of Hook1 have suggested a role in the maturation and trafficking of internalized proteins to the late endosome [12].
• However, mutation of CLN3 could lead to alterations in the functioning and positioning of organelles and membrane proteins through this Hook1-Ankyrin G interaction [12].
• Up to 60 backcross progeny were typed for azh, by microscopic examination of sperm heads, and for other markers [7].
• The azh (abnormal spermatozoon headshape) mutation in the mouse, which results in abnormal sperm head formation, was demonstrated to display an autosomal recessive pattern of inheritance [7].
• Sperm with abnormalities in the position and shape of the head were obtained from the azh/azh mutant and injected into the cytoplasm of mature mouse oocytes to determine whether sperm from the offspring display both head (club shape) and tail (looping, folding, and fusion) abnormalities observed in the mutant donor [8].

Associations of Hook1 with chemical compounds

• In addition, there are indications using certain compounds (cytoxan and 5-fluorouracil) as well as in the azh and sys mouse that the manchette may exert pressure to deform the nucleus [13].
• Celastrol, an active compound extracted from the root bark of the Chinese medicine "Thunder of God Vine" (Tripterygium wilfordii Hook F.), was used for years as a natural remedy for inflammatory conditions [14].
• Previous studies established that the platelet endoglucuronidase can degrade the exclusively N-sulfated as well as the N- and O-sulfated heparin precursor polysaccharides (Oldberg, A., Heldin, C.-H., Wasteson, A., Busch, C., and Höök, M. (1980) Biochemistry 19, 5755-5762) [15].
• It has previously been shown that the sulfation of liver heparan sulfate is lowered in diabetes (Kjellén, L., Bielefeld, D., and Höök, M. (1983) Diabetes 32, 337-342) [16].
• Evaluation of hepatoprotective effects of Helminthostachys zeylanica (L.) Hook against carbon tetrachloride-induced liver damage in Wistar rats [17].

Other interactions of Hook1

• Glucose 6-phosphate dehydrogenase-1 (Gpd-1), located on the distal part of chromosome 4, showed 26% recombination frequency with azh, indicating significant linkage (P less than .001) [7].
• We have found that: (1) Fractionated manchettes of azh/azh mutants are longer than in wild-type mice; (2) Manchette and sperm tail axonemes display a remarkable variety of posttranslationally modified tubulins (acetylated, glutamylated, tyrosinated, alpha-3/7 tubulins) [10].
• In addition, sys and azh mutant mice were used to determine the consequences of defective manchette formation [13].

Analytical, diagnostic and therapeutic context of Hook1

• A study of manchette development during spermiogenesis in azh/azh mutant mice was carried out by thin-section transmission electron microscopy with the goal of determining which of the initial steps in spermatid development are aberrant [18].
• Inhibition of type II collagen induced arthritis in mice by an immunosuppressive extract of Tripterygium wilfordii Hook f [19].
• Triptolide, an active component purified from the medicinal plant Tripterygium wilfordii Hook F., is potent in anti-inflammation and immunosuppression [20].
• Suppressive effects of Tripterygium wilfordii Hook f., a traditional Chinese medicine, on collagen arthritis in mice [21].

References