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Gene Review

Hexb  -  hexosaminidase B

Mus musculus

Synonyms: Beta-N-acetylhexosaminidase subunit beta, Beta-hexosaminidase subunit beta, Hexosaminidase subunit B, N-acetyl-beta-glucosaminidase subunit beta
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Disease relevance of Hexb

  • Hexa -/- mice suffer no obvious behavioral or neurological deficit, while Hexb -/- mice develop a fatal neurodegenerative disease, with spasticity, muscle weakness, rigidity, tremor and ataxia [1].
  • Mice containing a disruption of the Hexb gene have provided a useful model system for the study of the human lysosomal storage disorder known as Sandhoff disease (SD) [2].
  • To determine the role of these autoantibodies, the Fc receptor gamma gene (FcR gamma) was additionally disrupted in Hexb(-/-) mice, as it plays a key role in immune complex-mediated autoimmune diseases [2].
  • Oral glucose tolerance (OGTT), glucosyltransferase and N-acetyl-beta-glucosaminidase (enzymes involved in synthesis and degradation of kidney glycoproteins, respectively) in the kidney and serum, 24-hr proteinuria, and light microscopy studies of the kidney were performed [3].

High impact information on Hexb

  • Each gene encodes a subunit for the heterodimeric lysosomal enzyme, beta-hexosaminidase A (alpha beta), as well as for the homodimers beta-hexosaminidase B (beta beta) and S (alpha alpha) [4].
  • Through disruption of the Hexa and Hexb genes in embryonic stem cells, we have established mouse models corresponding to each disease [5].
  • We previously have described mouse models of Tay-Sachs (Hexa -/-) and Sandhoff (Hexb -/-) diseases with vastly different clinical phenotypes [6].
  • We have also been able to establish a syntenic relationship between the gene locus responsible for the expression of hexosaminidase A and those responsible for mannosephosphate isomerase and pyruvate kinase-3 and to assign the gene for hexosaminidase B to chromosome 5 in man [7].
  • Here we find that neuron death in Hexb-/- mice is associated with apoptosis occurring throughout the CNS, while Hexa-/- mice were minimally involved at the same age [8].

Chemical compound and disease context of Hexb


Biological context of Hexb

  • To explain the extensive epididymal abnormalities in the Hexb-/- mice, we propose that substrates for Hex, such as testis-derived glycolipids, cannot be catabolized and accumulate in lysosomes, leading to epididymal dysfunction and abnormalities in the epididymal luminal environment that supports sperm maturation [10].
  • The functional significance of these findings was established by the enhanced sensitivity of neurons cultured from embryonic Hexb-/- mice to cell death induced by thapsigargin, a specific SERCA inhibitor, and by the enhanced sensitivity of Hexb-/- microsomes to calcium-induced calcium release [11].
  • The ovarian function of Hexb(-/-) females was determined by superovulation studies [12].
  • Since both the Hexb (-/-) sexes showed fertility, the results indicate that Hex A and Hex B (major isozymes of beta-hexosaminidase) may not be required for sperm-ovum interactions, in contrast to the widely accepted belief [12].
  • Onset of symptoms correlated with reduced up-regulation of hexosaminidase B, a component of the bypass pathway [13].

Anatomical context of Hexb

  • The Hexb -/- but not the Hexa -/- mice have massive depletion of spinal cord axons as an apparent consequence of neuronal storage of GM2 [1].
  • In Hexb-/- mice (Hex A and B-deficient), the epididymal defects were much more extensive and the cytoplasm of all cell types throughout the efferent ducts and epididymis was filled with pale, uncondensed, enlarged lysosomes [10].
  • The extensive abnormalities in the Hexb-/- mice, in contrast to region-specific effects in the Hexa-/-mice, indicate an important and novel role for the Hex B isozyme in the epididymis and a region-specific role for Hex A in the initial segment/intermediate zone [10].
  • At 1 and 3 months of age, the testes, efferent ducts, and epididymides of Hex-deficient (Hexb -/-) and wild-type (Hexb +/+) mice were perfuse fixed and analyzed by routine light and electron microscopy (LM and EM, respectively) as well as with immunocytochemistry employing antibodies to lysosomal proteins [14].
  • In the testis, the morphological appearance and topographical arrangement of the cell types of the seminiferous epithelium of Hexb -/- mice were similar to those of wild-type animals at both ages [14].

Associations of Hexb with chemical compounds


Other interactions of Hexb


Analytical, diagnostic and therapeutic context of Hexb


  1. Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases. Phaneuf, D., Wakamatsu, N., Huang, J.Q., Borowski, A., Peterson, A.C., Fortunato, S.R., Ritter, G., Igdoura, S.A., Morales, C.R., Benoit, G., Akerman, B.R., Leclerc, D., Hanai, N., Marth, J.D., Trasler, J.M., Gravel, R.A. Hum. Mol. Genet. (1996) [Pubmed]
  2. Possible role of autoantibodies in the pathophysiology of GM2 gangliosidoses. Yamaguchi, A., Katsuyama, K., Nagahama, K., Takai, T., Aoki, I., Yamanaka, S. J. Clin. Invest. (2004) [Pubmed]
  3. Diabetic microangiopathy in KK mice. VI. Effect of glycemic control on renal glycoprotein metabolism and established glomerulosclerosis. Reddi, A.S., Velasco, C.A., Reddy, P.R., Khan, M.Y., Camerini-Davalos, R.A. Exp. Mol. Pathol. (1990) [Pubmed]
  4. Mice lacking both subunits of lysosomal beta-hexosaminidase display gangliosidosis and mucopolysaccharidosis. Sango, K., McDonald, M.P., Crawley, J.N., Mack, M.L., Tifft, C.J., Skop, E., Starr, C.M., Hoffmann, A., Sandhoff, K., Suzuki, K., Proia, R.L. Nat. Genet. (1996) [Pubmed]
  5. Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism. Sango, K., Yamanaka, S., Hoffmann, A., Okuda, Y., Grinberg, A., Westphal, H., McDonald, M.P., Crawley, J.N., Sandhoff, K., Suzuki, K., Proia, R.L. Nat. Genet. (1995) [Pubmed]
  6. Mouse model of GM2 activator deficiency manifests cerebellar pathology and motor impairment. Liu, Y., Hoffmann, A., Grinberg, A., Westphal, H., McDonald, M.P., Miller, K.M., Crawley, J.N., Sandhoff, K., Suzuki, K., Proia, R.L. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  7. Tay-Sachs' and Sandhoff's diseases: the assignment of genes for hexosaminidase A and B to individual human chromosomes. Gilbert, F., Kucherlapati, R., Creagan, R.P., Murnane, M.J., Darlington, G.J., Ruddle, F.H. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
  8. Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases. Huang, J.Q., Trasler, J.M., Igdoura, S., Michaud, J., Hanal, N., Gravel, R.A. Hum. Mol. Genet. (1997) [Pubmed]
  9. Elevation of lung surfactant phosphatidylcholine in mouse models of Sandhoff and of Niemann-Pick A disease. Buccoliero, R., Ginzburg, L., Futerman, A.H. J. Inherit. Metab. Dis. (2004) [Pubmed]
  10. Characterization of the testis and epididymis in mouse models of human Tay Sachs and Sandhoff diseases and partial determination of accumulated gangliosides. Trasler, J., Saberi, F., Somani, I.H., Adamali, H.I., Huang, J.Q., Fortunato, S.R., Ritter, G., Gu, M., Aebersold, R., Gravel, R.A., Hermo, L. Endocrinology (1998) [Pubmed]
  11. Inhibition of calcium uptake via the sarco/endoplasmic reticulum Ca2+-ATPase in a mouse model of Sandhoff disease and prevention by treatment with N-butyldeoxynojirimycin. Pelled, D., Lloyd-Evans, E., Riebeling, C., Jeyakumar, M., Platt, F.M., Futerman, A.H. J. Biol. Chem. (2003) [Pubmed]
  12. Development of infertility at young adult age in a mouse model of human Sandhoff disease. Juneja, S.C. Reprod. Fertil. Dev. (2002) [Pubmed]
  13. An inducible mouse model of late onset Tay-Sachs disease. Jeyakumar, M., Smith, D., Eliott-Smith, E., Cortina-Borja, M., Reinkensmeier, G., Butters, T.D., Lemm, T., Sandhoff, K., Perry, V.H., Dwek, R.A., Platt, F.M. Neurobiol. Dis. (2002) [Pubmed]
  14. I. Abnormalities in cells of the testis, efferent ducts, and epididymis in juvenile and adult mice with beta-hexosaminidase A and B deficiency. Adamali, H.I., Somani, I.H., Huang, J.Q., Mahuran, D., Gravel, R.A., Trasler, J.M., Hermo, L. J. Androl. (1999) [Pubmed]
  15. Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice. Denny, C.A., Kasperzyk, J.L., Gorham, K.N., Bronson, R.T., Seyfried, T.N. J. Neurosci. Res. (2006) [Pubmed]
  16. The use of urinary N-acetyl-beta-glucosaminidase in human renal toxicology. II. Elevation in human excretion after aspirin and sodium salicylate. Lockwood, T.D., Bosmann, H.B. Toxicol. Appl. Pharmacol. (1979) [Pubmed]
  17. Reduction of N-acetyl-beta-glucosaminidase activity in the submaxillary glands of streptozotocin diabetic mice. Hatakeyama, K., Hiramatsu, M., Minami, N. J. Biochem. (1980) [Pubmed]
  18. Assignment of genes encoding dihydrofolate reductase and hexosaminidase B to Mus musculus chromosome 13. Killary, A.M., Leach, R.J., Moran, R.G., Fournier, R.E. Somat. Cell Mol. Genet. (1986) [Pubmed]
  19. Analyses of bronchoalveolar lavage fluid (BALF) in MRL-lpr/lpr mice. Takaishi, M., Awaya, Y., Ishioka, S., Hozawa, S., Oyama, T., Takahashi, K., Maeda, H., Yamakido, M. Autoimmunity (1991) [Pubmed]
  20. Lysosomal enzymes in experimental diabetic cardiomyopathy. Giacomelli, F., Skoza, L., Wiener, J. Clin. Biochem. (1980) [Pubmed]
  21. Sperm require beta-N-acetylglucosaminidase to penetrate through the egg zona pellucida. Miller, D.J., Gong, X., Shur, B.D. Development (1993) [Pubmed]
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