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Gene Review

GUSB  -  glucuronidase, beta

Homo sapiens

Synonyms: BG, Beta-G1, Beta-glucuronidase, MPS7
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Disease relevance of GUSB

  • Deficiency of GUSB causes the lysosomal storage disease mucopolysaccharidosis VII (MPS VII, Sly disease) [1].
  • Both lines had morphologically similar widespread lysosomal storage of GUSB and secondary elevations of other lysosomal enzymes, a finding characteristic of lysosomal storage disease [1].
  • Gene therapy in MPS VII patients and animals may result in massive overexpression of GUSB in individual tissues, and the toxicity of such overexpression is incompletely investigated [1].
  • To investigate the effects of reducing lysosomal storage in nervous tissues, we injected recombinant adeno-associated virus encoding GUSB directly into the vitreous humor of young adult mice [2].
  • An important difference in clinical efficacy emerged in that phosphorylated GUSB was more efficient than non-phosphorylated enzyme at preventing the hearing loss associated with this disease [3].

Psychiatry related information on GUSB


High impact information on GUSB

  • GUSB activity in other organs was 1.5-60% of normal at 6 months for two RV-treated dogs, which was likely because of uptake of enzyme from blood by the mannose 6-phosphate receptor [5].
  • We present evidence that a 480G-->A transition in the coding region of the beta-glucuronidase gene, which results in an aspartic-acid-to-asparagine substitution at amino acid position 152 (D152N), produces a pseudodeficiency allele (GUSBp) that leads to greatly reduced levels of beta-glucuronidase activity without apparent deleterious consequences [6].
  • These findings demonstrate that the GUSB transgene is expressed in gusmps/gusmps mice and that human beta-glucuronidase corrects the murine mucopolysaccharidosis storage disease [7].
  • Immuno-affinity enrichment of stem and progenitor cells of 5- to 10-fold resulted in significantly higher GUSB activities at 2 months of age, but by 6 months engraftment was about 0.1% [8].
  • Nevertheless, GUSB expressed during the first 2 months of life in MPS VII fetuses could delay the onset of overt signs of disease [8].

Biological context of GUSB

  • The human lysosomal enzyme beta-glucuronidase (GUSB) was used as a reporter gene, because it can be distinguished from feline GUSB by heat stability [9].
  • However, the binding appears not to involve the active site of the human egasyn (hEg) and does not involve the C-terminal 18 amino acids of hGUSB [10].
  • Twelve weeks posttransplantation, lymphomyeloid expression of GUSB was detected in 10.8 +/- 1.6% of the human cells in the bone marrow with an average of 1 to 2 vector genomes measured per positive cell [11].
  • GUSB expression was increased to several times greater than normal by inserting the minigene into a double-copy vector (DCH beta H), which places one copy of the transcription unit upstream of the retrovirus promoter in both the 3' and 5' long terminal repeats (LTRs) of the integrated provirus [12].
  • The levels of GUSB in cells corrected with this vector exhibited the same cell density dependent pattern as when the GUSB promoter was used, indicating that the variation in enzymatic activity was not a function of the GUSB promoter.(ABSTRACT TRUNCATED AT 250 WORDS)[12]

Anatomical context of GUSB

  • RESULTS AND CONCLUSIONS: In our dataset, GUSB and CLK2 were the best choices as reference genes for EBV-LCLs and fibroblasts, respectively [13].
  • The deficiency of GUSB causes progressive accumulation of GAGs and subsequent lysosomal distension in multiple tissues, including the central nervous system (CNS) [14].
  • At 8-12 weeks after treatment, increased GUSB activity and reduced lysosomal distension were found in regions of the thalamus and tectum that received inputs from the injected eye [2].
  • The intracellular hEg coimmunoprecipitated with full-length hGUSB and with a truncated hGUSB missing the C-terminal 18-amino-acid residue when extracts of COS cells expressing both proteins were treated with anti-hGUSB antibody [10].
  • Transplantation in utero of either syngeneic fetal liver hematopoietic stem cells marked with a retroviral vector, or allogeneic donor cells that constitutively express high levels of human GUSB from a transgene, resulted in only about 0.1% engraftment in the adult [8].

Associations of GUSB with chemical compounds


Other interactions of GUSB

  • The following markers and syntenic groups were localized : GUSB on PPA3 ; NP-MPI-PKM2-IDH2 on PPA7; ADA on PPA10 and IDH1 on PPA12 [19].
  • We obtained evidence for a gene dosage effect for GUSB, but not for PSP [20].
  • The specific activity of GUSB and a control normal lysosomal enzyme, alpha-galactosidase (GLA), were higher in normal and in vector-corrected cells from confluent cultures than in subconfluent dividing cells [12].
  • In this study, the efficacy of gene therapy targeted to human hematopoietic progenitor cells was investigated for mucopolysaccharidosis type VII (MPSVII), a LSD caused by beta-glucuronidase (GUSB) deficiency [11].
  • GenBank sequence analyses showed that the CpG island of human GUSB is juxtaposed with multiple Alu repeats and also includes multiple Sp1 sites upstream and downstream of the transcription start, which has been suggested to prevent CpG islands from becoming methylated [15].

Analytical, diagnostic and therapeutic context of GUSB

  • Newborn MPS VII mice received a single intravenous injection with 5.4 x 10(6) infectious units of recombinant adeno-associated virus encoding the human beta-glucuronidase (GUSB) cDNA [21].
  • Therefore, GUSB-deficient mobilized peripheral blood CD34(+) cells from a patient with MPSVII were transduced with a third-generation lentiviral vector encoding human GUSB and then assessed in a xenotransplantation system [11].
  • Total or poly A(+)-RNA isolated from cells or tissues of different species were examined in Northern blots to identify GUSB mRNA transcripts [22].
  • The gene coding for human beta-glucuronidase (GUSB) was mapped to 7q11.21 --> q11.22 by fluorescence in situ hybridization (FISH), thus clarifying the contradictory published localizations of this gene [23].
  • In western blot analysis using anti-human GUSB antibody, three bands of size 78, 56, and 38 kDa were detected in normal samples, which were present at lower intensity in the carrier RPE samples and absent in the MPS VII-affected RPE samples [17].


  1. Transgene produces massive overexpression of human beta -glucuronidase in mice, lysosomal storage of enzyme, and strain-dependent tumors. Vogler, C., Galvin, N., Levy, B., Grubb, J., Jiang, J., Zhou, X.Y., Sly, W.S. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  2. Intravitreal gene therapy reduces lysosomal storage in specific areas of the CNS in mucopolysaccharidosis VII mice. Hennig, A.K., Levy, B., Ogilvie, J.M., Vogler, C.A., Galvin, N., Bassnett, S., Sands, M.S. J. Neurosci. (2003) [Pubmed]
  3. Biodistribution, kinetics, and efficacy of highly phosphorylated and non-phosphorylated beta-glucuronidase in the murine model of mucopolysaccharidosis VII. Sands, M.S., Vogler, C.A., Ohlemiller, K.K., Roberts, M.S., Grubb, J.H., Levy, B., Sly, W.S. J. Biol. Chem. (2001) [Pubmed]
  4. Decreased lysosomal storage in the adult MPS VII mouse brain in the vicinity of grafts of retroviral vector-corrected fibroblasts secreting high levels of beta-glucuronidase. Taylor, R.M., Wolfe, J.H. Nat. Med. (1997) [Pubmed]
  5. Therapeutic neonatal hepatic gene therapy in mucopolysaccharidosis VII dogs. Ponder, K.P., Melniczek, J.R., Xu, L., Weil, M.A., O'Malley, T.M., O'Donnell, P.A., Knox, V.W., Aguirre, G.D., Mazrier, H., Ellinwood, N.M., Sleeper, M., Maguire, A.M., Volk, S.W., Mango, R.L., Zweigle, J., Wolfe, J.H., Haskins, M.E. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  6. A pseudodeficiency allele (D152N) of the human beta-glucuronidase gene. Vervoort, R., Islam, M.R., Sly, W., Chabas, A., Wevers, R., de Jong, J., Liebaers, I., Lissens, W. Am. J. Hum. Genet. (1995) [Pubmed]
  7. Correction of murine mucopolysaccharidosis VII by a human beta-glucuronidase transgene. Kyle, J.W., Birkenmeier, E.H., Gwynn, B., Vogler, C., Hoppe, P.C., Hoffmann, J.W., Sly, W.S. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  8. In utero transplantation of fetal liver cells in the mucopolysaccharidosis type VII mouse results in low-level chimerism, but overexpression of beta-glucuronidase can delay onset of clinical signs. Casal, M.L., Wolfe, J.H. Blood (2001) [Pubmed]
  9. Adeno-associated virus vector-mediated transduction in the cat brain. Vite, C.H., Passini, M.A., Haskins, M.E., Wolfe, J.H. Gene Ther. (2003) [Pubmed]
  10. Human egasyn binds beta-glucuronidase but neither the esterase active site of egasyn nor the C terminus of beta-glucuronidase is involved in their interaction. Islam, M.R., Waheed, A., Shah, G.N., Tomatsu, S., Sly, W.S. Arch. Biochem. Biophys. (1999) [Pubmed]
  11. Human CD34+ hematopoietic progenitor cell-directed lentiviral-mediated gene therapy in a xenotransplantation model of lysosomal storage disease. Hofling, A.A., Devine, S., Vogler, C., Sands, M.S. Mol. Ther. (2004) [Pubmed]
  12. High level expression and export of beta-glucuronidase from murine mucopolysaccharidosis VII cells corrected by a double-copy retrovirus vector. Wolfe, J.H., Kyle, J.W., Sands, M.S., Sly, W.S., Markowitz, D.G., Parente, M.K. Gene Ther. (1995) [Pubmed]
  13. Comparison of 12 reference genes for normalization of gene expression levels in Epstein-Barr virus-transformed lymphoblastoid cell lines and fibroblasts. de Brouwer, A.P., van Bokhoven, H., Kremer, H. Molecular diagnosis & therapy. (2006) [Pubmed]
  14. Encapsulation cell therapy for mucopolysaccharidosis type VII using genetically engineered immortalized human amniotic epithelial cells. Nakama, H., Ohsugi, K., Otsuki, T., Date, I., Kosuga, M., Okuyama, T., Sakuragawa, N. Tohoku J. Exp. Med. (2006) [Pubmed]
  15. Methylation patterns of the human beta-glucuronidase gene locus: boundaries of methylation and general implications for frequent point mutations at CpG dinucleotides. Tomatsu, S., Orii, K.O., Islam, M.R., Shah, G.N., Grubb, J.H., Sukegawa, K., Suzuki, Y., Orii, T., Kondo, N., Sly, W.S. Genomics (2002) [Pubmed]
  16. Phenotype correction in murine mucopolysaccharidosis type VII by transplantation of human amniotic epithelial cells after adenovirus-mediated gene transfer. Kosuga, M., Takahashi, S., Sasaki, K., Enosawa, S., Li, X.K., Okuyama, S., Fujino, M., Suzuki, S., Yamada, M., Matsuo, N., Sakuragawa, N., Okuyama, T. Cell transplantation. (2000) [Pubmed]
  17. Biochemical basis of the beta-glucuronidase gene defect causing canine mucopolysaccharidosis VII. Ray, J., Scarpino, V., Laing, C., Haskins, M.E. J. Hered. (1999) [Pubmed]
  18. Active site residues of human beta-glucuronidase. Evidence for Glu(540) as the nucleophile and Glu(451) as the acid-base residue. Islam, M.R., Tomatsu, S., Shah, G.N., Grubb, J.H., Jain, S., Sly, W.S. J. Biol. Chem. (1999) [Pubmed]
  19. Comparative gene mapping of the baboon (Papio papio) and man. Créau-Goldberg, N., Turleau, C., Cochet, C., de Grouchy, J. Ann. Genet. (1982) [Pubmed]
  20. Gene dosage effect in acquired monosomy 7: distinct behaviour of beta-glucuronidase and phosphoserine phosphatase. Minelli, A., Piantanida, M., Maserati, E., Campagnoli, E., Pasquali, F., Danesino, C. Genes Chromosomes Cancer (1990) [Pubmed]
  21. Neonatal gene transfer leads to widespread correction of pathology in a murine model of lysosomal storage disease. Daly, T.M., Vogler, C., Levy, B., Haskins, M.E., Sands, M.S. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  22. Characterization of beta-glucuronidase in the retinal pigment epithelium. Ray, J., Wu, Y., Aguirre, G.D. Curr. Eye Res. (1997) [Pubmed]
  23. Localization by fluorescence in situ hybridization of the human functional beta-glucuronidase gene (GUSB) to 7q11.21 --> q11.22 and two pseudogenes to 5p13 and 5q13. Speleman, F., Vervoort, R., van Roy, N., Liebaers, I., Sly, W.S., Lissens, W. Cytogenet. Cell Genet. (1996) [Pubmed]
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