Gba

Summary

Gene Symbol: Gba
Description: glucosidase, beta, acid
Alias: GBA1, GCase, GLUC, betaGC, glucosylceramidase, D-glucosyl-N-acylsphingosine glucohydrolase, acid beta glucosidase, beta-glucocerebrosidase, glucocerebrosidase
Species: mouse

Top Publications

  1. ncbi Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion
    S F Kingsmore
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710
    Nat Genet 7:136-41. 1994
  2. pmc Specific saposin C deficiency: CNS impairment and acid beta-glucosidase effects in the mouse
    Ying Sun
    Division of Human Genetics, Cincinnati Children s Hospital Medical Center, Cincinnati, OH, USA
    Hum Mol Genet 19:634-47. 2010
  3. doi Spatial and temporal correlation between neuron loss and neuroinflammation in a mouse model of neuronopathic Gaucher disease
    Tamar Farfel-Becker
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Hum Mol Genet 20:1375-86. 2011
  4. pmc Global gene expression profile progression in Gaucher disease mouse models
    You Hai Xu
    The Division of Human Genetics, Cincinnati Children s Hospital Research Foundation, Cincinnati, OH 45229 3039, USA
    BMC Genomics 12:20. 2011
  5. pmc Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage
    Pramod K Mistry
    Department of Pediatrics, Yale School of Medicine, New Haven, CT 06562, USA
    Proc Natl Acad Sci U S A 107:19473-8. 2010
  6. doi Intracerebroventricular delivery of glucocerebrosidase reduces substrates and increases lifespan in a mouse model of neuronopathic Gaucher disease
    M A Cabrera-Salazar
    Genzyme Corporation, Framingham, MA 01701, USA
    Exp Neurol 225:436-44. 2010
  7. doi Altered expression and distribution of cathepsins in neuronopathic forms of Gaucher disease and in other sphingolipidoses
    Einat B Vitner
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
    Hum Mol Genet 19:3583-90. 2010
  8. pmc Mice with type 2 and 3 Gaucher disease point mutations generated by a single insertion mutagenesis procedure
    Y Liu
    Section on Biochemical Genetics, Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 95:2503-8. 1998
  9. ncbi Accumulation of protein-bound epidermal glucosylceramides in beta-glucocerebrosidase deficient type 2 Gaucher mice
    T Doering
    Kekule Institut fur Organische Chemie und Biochemie, Universitat Bonn, Germany
    FEBS Lett 447:167-70. 1999
  10. pmc The pharmacological chaperone isofagomine increases the activity of the Gaucher disease L444P mutant form of beta-glucosidase
    Richie Khanna
    Amicus Therapeutics, Cranbury, NJ, USA
    FEBS J 277:1618-38. 2010

Research Grants

  1. INBORN ERRORS OF SPHINGOLIPID CATABOLISM
    Gregory Grabowski; Fiscal Year: 2004
  2. Use of Hammerhead Ribozymes in Murine Models of Ol
    Gregory Grabowski; Fiscal Year: 2007
  3. Studies of Prosaposin's Physiologic Role
    Gregory Grabowski; Fiscal Year: 2007

Scientific Experts

  • S Pablo Sardi
  • M A Cabrera-Salazar
  • Robert L Nussbaum
  • Atul Mehta
  • Yildiz Yildiz
  • Carmen A Argmann
  • Gregory Grabowski
  • Pramod K Mistry
  • David Reczek
  • M Schmuth
  • Ying Sun
  • You Hai Xu
  • Brian Quinn
  • Wujuan Zhang
  • Einat B Vitner
  • Tamar Farfel-Becker
  • Kenneth D R Setchell
  • Manoj Kumar Pandey
  • Benjamin Liou
  • Anthony H Futerman
  • David P Witte
  • Ida Berglin Enquist
  • David Witte
  • Stefan Karlsson
  • Edward I Ginns
  • Jorge F Haller
  • Hisako Akiyama
  • Tatyana A Shelkovnikova
  • Monica Di Giacomo
  • Jun Liu
  • Klaus Harzer
  • Ellen Sidransky
  • Y H Xu
  • Joseph R Mazzulli
  • Raya Eilam
  • Yusuf A Hannun
  • Charles V Vorhees
  • Kazuyuki Kitatani
  • Matthew R Skelton
  • Huimin Ran
  • Michael T Williams
  • Richie Khanna
  • Wei Lien Chuang
  • Marielle Boonen
  • Graham B Sinclair
  • Kerry Anne McEachern
  • Roscoe O Brady
  • Johan Richter
  • Mats Ehinger
  • Eva Nilsson
  • Jan Eric Mansson
  • Andreas Ooka
  • Eun Young Kim
  • C A Kozak
  • Rie Uematsu
  • Yutaka Takagi
  • Saadia A Karim
  • Rong hua Li
  • Juliane Karlgren
  • Yin Guo
  • Vivian P Chou
  • Andres D Klein
  • Mason W Freeman
  • Mary L Lamarca
  • Paul Cavallaro
  • Lee Dolat
  • Michael L Fitzgerald
  • Stephanie J Soscia
  • Nicholas J Hernandez
  • Mohammad Ali
  • Schahram Akbarian
  • Ruth Welti
  • Steven Samuelsson
  • Nicholas A Jabre
  • Hiroki Mizukami
  • Ling Xue
  • Amy B Manning-Bog
  • Arlene Lim
  • Frances M Platt
  • Novie Ko
  • Anna Meshcheriakova
  • Timothy M Cox
  • Ran Salomon
  • Sally K K Mak
  • Kui Xu
  • Jacqueline Vazquez-Derose
  • Lina Vasiliauskaite
  • Elena R Sadchikova
  • Anton J Enright
  • Veronica I Skvortsova

Detail Information

Publications83

  1. ncbi Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion
    S F Kingsmore
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710
    Nat Genet 7:136-41. 1994
    ..These results provide evidence that Glrb is necessary for postsynaptic expression of glycine receptor complexes, and suggest Glrb as a candidate gene for inherited myoclonus in other species...
  2. pmc Specific saposin C deficiency: CNS impairment and acid beta-glucosidase effects in the mouse
    Ying Sun
    Division of Human Genetics, Cincinnati Children s Hospital Medical Center, Cincinnati, OH, USA
    Hum Mol Genet 19:634-47. 2010
    ..system (CNS) phenotype attributed to diminished glucosylceramide (GC) cleavage activity by acid beta-glucosidase (GCase)...
  3. doi Spatial and temporal correlation between neuron loss and neuroinflammation in a mouse model of neuronopathic Gaucher disease
    Tamar Farfel-Becker
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Hum Mol Genet 20:1375-86. 2011
    ..disease (GD), the most common lysosomal storage disorder, is caused by a deficiency in the lysosomal enzyme glucocerebrosidase (GlcCerase), which results in intracellular accumulation of glucosylceramide (GlcCer)...
  4. pmc Global gene expression profile progression in Gaucher disease mouse models
    You Hai Xu
    The Division of Human Genetics, Cincinnati Children s Hospital Research Foundation, Cincinnati, OH 45229 3039, USA
    BMC Genomics 12:20. 2011
    Gaucher disease is caused by defective glucocerebrosidase activity and the consequent accumulation of glucosylceramide...
  5. pmc Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage
    Pramod K Mistry
    Department of Pediatrics, Yale School of Medicine, New Haven, CT 06562, USA
    Proc Natl Acad Sci U S A 107:19473-8. 2010
    In nonneuronopathic type 1 Gaucher disease (GD1), mutations in the glucocerebrosidase gene (GBA1) gene result in glucocerebrosidase deficiency and the accumulation of its substrate, glucocerebroside (GL-1), in the lysosomes of mononuclear ..
  6. doi Intracerebroventricular delivery of glucocerebrosidase reduces substrates and increases lifespan in a mouse model of neuronopathic Gaucher disease
    M A Cabrera-Salazar
    Genzyme Corporation, Framingham, MA 01701, USA
    Exp Neurol 225:436-44. 2010
    Gaucher disease is caused by a deficit in the enzyme glucocerebrosidase. As a consequence, degradation of the glycolipids glucosylceramide (GluCer) and glucosylsphingosine (GluSph) is impaired, and their subsequent buildup can lead to ..
  7. doi Altered expression and distribution of cathepsins in neuronopathic forms of Gaucher disease and in other sphingolipidoses
    Einat B Vitner
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
    Hum Mol Genet 19:3583-90. 2010
    ..Recently, a mouse model of neuronopathic GD was generated in which glucocerebrosidase deficiency is limited to neural and glial progenitor cells...
  8. pmc Mice with type 2 and 3 Gaucher disease point mutations generated by a single insertion mutagenesis procedure
    Y Liu
    Section on Biochemical Genetics, Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 95:2503-8. 1998
    Gaucher disease is caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GC)...
  9. ncbi Accumulation of protein-bound epidermal glucosylceramides in beta-glucocerebrosidase deficient type 2 Gaucher mice
    T Doering
    Kekule Institut fur Organische Chemie und Biochemie, Universitat Bonn, Germany
    FEBS Lett 447:167-70. 1999
    ..membranes, derive in large part from hydrolysis of glucosylceramides mediated by the lysosomal enzyme beta-glucocerebrosidase. As analyzed in this work, the beta-glucocerebrosidase deficiency in type 2 Gaucher mice (RecNci I) resulted ..
  10. pmc The pharmacological chaperone isofagomine increases the activity of the Gaucher disease L444P mutant form of beta-glucosidase
    Richie Khanna
    Amicus Therapeutics, Cranbury, NJ, USA
    FEBS J 277:1618-38. 2010
    Gaucher disease is caused by mutations in the gene that encodes the lysosomal enzyme acid beta-glucosidase (GCase)...
  11. ncbi Glucosylsphingosine accumulation in mice and patients with type 2 Gaucher disease begins early in gestation
    E Orvisky
    Clinical Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Marvland 20892 4405, USA
    Pediatr Res 48:233-7. 2000
    Gaucher disease, the most common of the sphingolipidoses, results from the inherited deficiency of the enzyme glucocerebrosidase (EC 3.2.1.45)...
  12. pmc Neuronopathic Gaucher disease in the mouse: viable combined selective saposin C deficiency and mutant glucocerebrosidase (V394L) mice with glucosylsphingosine and glucosylceramide accumulation and progressive neurological deficits
    Ying Sun
    The Division of Human Genetics, Cincinnati Children s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 3039, USA
    Hum Mol Genet 19:1088-97. 2010
    Gaucher disease is caused by defective acid beta-glucosidase (GCase) function. Saposin C is a lysosomal protein needed for optimal GCase activity...
  13. pmc Accumulation and distribution of α-synuclein and ubiquitin in the CNS of Gaucher disease mouse models
    Y H Xu
    Division of Human Genetics, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Mol Genet Metab 102:436-47. 2011
    Gaucher disease, a prevalent lysosomal storage disease, is caused by insufficient activity of acid β-glucosidase (GCase) and resultant glucosylceramide accumulation...
  14. pmc Systemic inflammation in glucocerebrosidase-deficient mice with minimal glucosylceramide storage
    Hiroki Mizukami
    Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Clin Invest 109:1215-21. 2002
    Gaucher disease, the most common lysosomal storage disease, is caused by a deficiency of glucocerebrosidase resulting in the impairment of glucosylceramide degradation...
  15. ncbi Saposin C is required for normal resistance of acid beta-glucosidase to proteolytic degradation
    Ying Sun
    Division and Program in Human Genetics, Children s Hospital Research Foundation, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 278:31918-23. 2003
    ..In the lysosomal sphingolipid degradation pathway, acid beta-glucosidase (GCase) requires saposin C for optimal in vitro and in vivo hydrolysis of glucocerebroside...
  16. pmc Viable mouse models of acid beta-glucosidase deficiency: the defect in Gaucher disease
    You Hai Xu
    Divisions of Human Genetics and Pathology, Cincinnati Children s Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio 45229 3039, USA
    Am J Pathol 163:2093-101. 2003
    Gaucher disease is an autosomal recessively inherited disease caused by mutations at the acid beta-glucosidase (GCase) locus (GBA)...
  17. pmc Dependence of reversibility and progression of mouse neuronopathic Gaucher disease on acid beta-glucosidase residual activity levels
    You Hai Xu
    The Divisions of Human Genetics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, MLC 4006, Cincinnati, OH 45229 3039, USA
    Mol Genet Metab 94:190-203. 2008
    ..The lethality of the skin permeability barrier defect of the complete gene knock out [gba, (glucocerebrosidase) GCase] was avoided by conditional reactivation of a low activity allele (D409H) in keratinocytes (kn-9H)...
  18. ncbi Gaucher disease mouse models: point mutations at the acid beta-glucosidase locus combined with low-level prosaposin expression lead to disease variants
    Ying Sun
    Division and Program in Human Genetics, Children s Hospital Research Foundation, Cincinnati, OH 45229 3039, USA
    J Lipid Res 46:2102-13. 2005
    Gaucher disease is a common lysosomal storage disease caused by a defect of acid beta-glucosidase (GCase)...
  19. ncbi A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease
    Kerry Anne McEachern
    Genzyme Corporation, 31 New York Avenue, Framingham, MA 01701 9322, USA
    Mol Genet Metab 91:259-67. 2007
    ..These data indicate that substrate inhibition therapy with Genz-112638 represents a viable alternate approach to enzyme therapy to treat the visceral pathology in Gaucher disease...
  20. ncbi Conditional expression of human acid beta-glucosidase improves the visceral phenotype in a Gaucher disease mouse model
    Ying Sun
    Division of Human Genetics, Children s Hospital Research Foundation and University of Cincinnati College of Medicine, Department of Pediatrics, Cincinnati, OH 45229 3039, USA
    J Lipid Res 47:2161-70. 2006
    ..4L/PS-NA has the acid beta-glucosidase (GCase) V394L/V394L (4L) point mutation combined with hypomorphic ( approximately 6% wild-type) expression of the mouse ..
  21. ncbi Downregulation of neurotrophic factors in the brain of a mouse model of Gaucher disease; implications for neuronal loss in Gaucher disease
    Eun Young Kim
    Department of Biomedical Sciences, National Institute of Health, Seoul 122 701, Korea
    Exp Mol Med 38:348-56. 2006
    Gaucher disease is a glycosphingolipid storage disease caused by deficiency of glucocerebrosidase, resulting in the accumulation of glucosylceramide in lysosomes...
  22. pmc Effective cell and gene therapy in a murine model of Gaucher disease
    Ida Berglin Enquist
    Department of Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine, and Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, BMC A12, 221 84 Lund, Sweden
    Proc Natl Acad Sci U S A 103:13819-24. 2006
    Gaucher disease (GD) is a lysosomal storage disorder due to an inherited deficiency in the enzyme glucosylceramidase (GCase) that causes hepatosplenomegaly, cytopenias, and bone disease as key clinical symptoms...
  23. ncbi Generation of a conditional knockout of murine glucocerebrosidase: utility for the study of Gaucher disease
    Graham B Sinclair
    Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 950 W28th Ave Vancouver, BC, Canada V5Z 4H4
    Mol Genet Metab 90:148-56. 2007
    ..is a disorder of sphingolipid metabolism resulting from an inherited deficiency of the lysosomal hydrolase glucocerebrosidase. Affected individuals present with a spectrum of clinical symptoms ranging from hepatosplenomegaly, ..
  24. pmc Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease
    W M Holleran
    Department of Dermatology, University of California School of Medicine, San Francisco 94143
    J Clin Invest 93:1756-64. 1994
    Hydrolysis of glucosylceramide by beta-glucocerebrosidase results in ceramide, a critical component of the intercellular lamellae that mediate the epidermal permeability barrier...
  25. pmc Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies
    Joseph R Mazzulli
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA 02129, USA
    Cell 146:37-52. 2011
    ..Here, we show that functional loss of GD-linked glucocerebrosidase (GCase) in primary cultures or human iPS neurons compromises lysosomal protein degradation, causes ..
  26. pmc CNS expression of glucocerebrosidase corrects alpha-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy
    S Pablo Sardi
    Genzyme Corporation, Framingham, MA 01701, USA
    Proc Natl Acad Sci U S A 108:12101-6. 2011
    ..and Gba1(+/-)) Gaucher mice indicated that these pathologies are a result of the combination of a loss of glucocerebrosidase activity and a toxic gain-of-function resulting from expression of the mutant enzyme...
  27. pmc Ex vivo and in vivo effects of isofagomine on acid β-glucosidase variants and substrate levels in Gaucher disease
    Ying Sun
    Division of Human Genetics, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 287:4275-87. 2012
    Isofagomine (IFG) is an acid β-glucosidase (GCase) active site inhibitor that acts as a pharmacological chaperone. The effect of IFG on GCase function was investigated in GCase mutant fibroblasts and mouse models...
  28. pmc Beta-glucosidase 1 (GBA1) is a second bile acid β-glucosidase in addition to β-glucosidase 2 (GBA2). Study in β-glucosidase deficient mice and humans
    Klaus Harzer
    Neurometabolic Laboratory, Klinik fur Kinder und Jugendmedizin, University of Tubingen, Tubingen, Germany
    Biochem Biophys Res Commun 423:308-12. 2012
    Beta-glucosidase 1 (GBA1; lysosomal glucocerebrosidase) and β-glucosidase 2 (GBA2, non-lysosomal glucocerebrosidase) both have glucosylceramide as a main natural substrate...
  29. ncbi A biochemical and ultrastructural evaluation of the type 2 Gaucher mouse
    R Willemsen
    Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands
    Mol Chem Neuropathol 24:179-92. 1995
    Gaucher mice, created by targeted disruption of the glucocerebrosidase gene, are totally deficient in glucocerebrosidase and have a rapidly deteriorating clinical course analogous to the most severely affected type 2 human patients...
  30. ncbi Animal model of Gaucher's disease from targeted disruption of the mouse glucocerebrosidase gene
    V L Tybulewicz
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142
    Nature 357:407-10. 1992
    ..lysosomal storage disorder in humans and results from an autosomally inherited deficiency of the enzyme glucocerebrosidase (beta-D-glucosyl-N-acylsphingosine glucohydrolase), which is responsible for degrading the sphingolipid ..
  31. doi RIPK3 as a potential therapeutic target for Gaucher's disease
    Einat B Vitner
    1 Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel 2
    Nat Med 20:204-8. 2014
    Gaucher's disease (GD), an inherited metabolic disorder caused by mutations in the glucocerebrosidase gene (GBA), is the most common lysosomal storage disease. Heterozygous mutations in GBA are a major risk factor for Parkinson's disease...
  32. pmc Comparison of the chromosomal localization of murine and human glucocerebrosidase genes and of the deduced amino acid sequences
    R R O'Neill
    Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 86:5049-53. 1989
    ..evolution, we determined the nucleotide sequence and chromosomal location of the gene encoding murine glucocerebrosidase (glucosylceramidase; D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45)...
  33. pmc Murine models of acute neuronopathic Gaucher disease
    Ida Berglin Enquist
    Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine and the Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, BMC A12, 221 84 Lund, Sweden
    Proc Natl Acad Sci U S A 104:17483-8. 2007
    ..disorder caused by mutations in the glucosidase, beta, acid (GBA) gene that encodes the lysosomal enzyme glucosylceramidase (GCase)...
  34. ncbi Murine VCAM-1. Molecular cloning, mapping, and analysis of a truncated form
    A G Kumar
    Department of Internal Medicine, Baylor College of Medicine, Houston, TX 77030
    J Immunol 153:4088-98. 1994
    ..Thus, expression of VCAM-1 is restricted and controlled at the level of transcription and by alternative splicing...
  35. pmc Glucocerebrosidase 2 gene deletion rescues type 1 Gaucher disease
    Pramod K Mistry
    Department of Medicine, Yale School of Medicine, New Haven, CT 06520
    Proc Natl Acad Sci U S A 111:4934-9. 2014
    The inherited deficiency of the lysosomal glucocerebrosidase (GBA) due to mutations in the GBA gene results in Gaucher disease (GD). A vast majority of patients present with nonneuronopathic, type 1 GD (GD1)...
  36. pmc A Next Generation Multiscale View of Inborn Errors of Metabolism
    Carmen A Argmann
    Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1498, New York, NY 10029, USA Electronic address
    Cell Metab 23:13-26. 2016
    ..We foresee that panomics and network strategies combined with recent experimental innovations will facilitate this. ..
  37. pmc Multiple pathogenic proteins implicated in neuronopathic Gaucher disease mice
    You Hai Xu
    The Division of Human Genetics and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
    Hum Mol Genet 23:3943-57. 2014
    ..disease, a prevalent lysosomal storage disease (LSD), is caused by insufficient activity of acid β-glucosidase (GCase) and the resultant glucosylceramide (GC)/glucosylsphingosine (GS) accumulation in visceral organs (Type 1) and the ..
  38. doi Neuroinflammation and α-synuclein accumulation in response to glucocerebrosidase deficiency are accompanied by synaptic dysfunction
    Edward I Ginns
    Lysosomal Disorders Treatment and Research Program, Clinical Labs, University of Massachusetts Medical School, Worcester, MA 01545, USA Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01545, USA Clinical Neuroscience Branch, IRP, NIMH, Bethesda, MD 20892, USA
    Mol Genet Metab 111:152-62. 2014
    ..In this report we describe and characterize two novel long-lived transgenic mouse models of Gba deficiency, along with a subchronic conduritol-ß-epoxide (CBE) exposure paradigm...
  39. pmc Endogenous β-glucocerebrosidase activity in Abca12⁻/⁻epidermis elevates ceramide levels after topical lipid application but does not restore barrier function
    Jorge F Haller
    Lipid Metabolism Unit and Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114
    J Lipid Res 55:493-503. 2014
    ..A defect was found in β-glucocerebrosidase (GCase) processing of newly synthesized GlcCer species. This was not due to a decline in GCase function...
  40. doi Cholesterol glucosylation is catalyzed by transglucosylation reaction of β-glucosidase 1
    Hisako Akiyama
    Graduate School of Humanities and Sciences, Department of Life Science, Ochanomizu University, 2 1 1 Ohtsuka, Bunkyo ku, Tokyo 112 8610, Japan Brain Science Institute, RIKEN, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Biochem Biophys Res Commun 441:838-43. 2013
    ..In this study, we examined the possibility of glucocerebrosidase, a GlcCer-degrading glycosidase, acting as β-ChlGlc-synthesizing enzyme...
  41. doi Gaucher disease: chemotactic factors and immunological cell invasion in a mouse model
    Manoj Kumar Pandey
    Division of Human Genetics, Cincinnati Children s Hospital Medical Center, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
    Mol Genet Metab 111:163-71. 2014
    Gaucher disease results from mutations in GBA1 that cause functional disruption of the encoded lysosomal enzyme, acid β-glucosidase...
  42. pmc Mice lacking mannose 6-phosphate uncovering enzyme activity have a milder phenotype than mice deficient for N-acetylglucosamine-1-phosphotransferase activity
    Marielle Boonen
    Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Mol Biol Cell 20:4381-9. 2009
    ....
  43. pmc Functional and genetic characterization of the non-lysosomal glucosylceramidase 2 as a modifier for Gaucher disease
    Yildiz Yildiz
    Department of Internal Medicine I, University Clinic of Bonn, Bonn, Germany
    Orphanet J Rare Dis 8:151. 2013
    ..lysosomal storage disorder in humans, caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBA1)...
  44. pmc Fused in sarcoma (FUS) protein lacking nuclear localization signal (NLS) and major RNA binding motifs triggers proteinopathy and severe motor phenotype in transgenic mice
    Tatyana A Shelkovnikova
    School of Biosciences, Cardiff University, Cardiff, Wales, United Kingdom
    J Biol Chem 288:25266-74. 2013
    ..Our data indicate that neuronal FUS aggregation is sufficient to cause ALS-like phenotype in transgenic mice. ..
  45. doi Multiple epigenetic mechanisms and the piRNA pathway enforce LINE1 silencing during adult spermatogenesis
    Monica Di Giacomo
    Mouse Biology Unit, European Molecular Biology Laboratory, Via Ramarini 32, 00015 Monterotondo Scalo, Italy
    Mol Cell 50:601-8. 2013
    ..We demonstrate the existence of multiple epigenetic mechanisms that in conjunction with the piRNA pathway sequentially enforce L1 silencing and genomic stability during mitotic and meiotic stages of adult spermatogenesis...
  46. pmc Augmenting CNS glucocerebrosidase activity as a therapeutic strategy for parkinsonism and other Gaucher-related synucleinopathies
    S Pablo Sardi
    Genzyme, a Sanofi Company, Framingham, MA 01701, USA
    Proc Natl Acad Sci U S A 110:3537-42. 2013
    Mutations of GBA1, the gene encoding glucocerebrosidase, represent a common genetic risk factor for developing the synucleinopathies Parkinson disease (PD) and dementia with Lewy bodies...
  47. pmc Gaucher disease gene GBA functions in immune regulation
    Jun Liu
    Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 109:10018-23. 2012
    Inherited deficiency of acid β-glucosidase (GCase) due to biallelic mutations in the GBA (glucosidase, β, acid) gene causes the classic manifestations of Gaucher disease (GD) involving the viscera, the skeleton, and the lungs...
  48. ncbi Definition of mouse chromosome 1 and 3 gene linkage groups that are conserved on human chromosome 1: evidence that a conserved linkage group spans the centromere of human chromosome 1
    W S Moseley
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710
    Genomics 5:899-905. 1989
    ..These studies provide a model for examination of specific evolutionary events...
  49. doi Mutant GBA1 expression and synucleinopathy risk: first insights from cellular and mouse models
    S Pablo Sardi
    Genzyme, Sanofi Company, Framingham, Mass 01701, USA
    Neurodegener Dis 10:195-202. 2012
    Heterozygous mutations in the glucocerebrosidase gene (GBA1) are associated with increased risk for α-synuclein aggregation disorders ('synucleinopathies'), which include Parkinson's disease (PD) and dementia with Lewy bodies (DLB)...
  50. pmc Immunological cell type characterization and Th1-Th17 cytokine production in a mouse model of Gaucher disease
    Manoj Kumar Pandey
    Division of Human Genetics, Cincinnati Children s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 3039, USA
    Mol Genet Metab 106:310-22. 2012
    Gaucher disease is a lysosomal storage disease resulting from insufficient acid β-glucosidase (glucocerebrosidase, GCase, EC 4.2.1.25) activity and the resultant accumulation of glucosylceramide...
  51. pmc Systemic delivery of a glucosylceramide synthase inhibitor reduces CNS substrates and increases lifespan in a mouse model of type 2 Gaucher disease
    Mario A Cabrera-Salazar
    Genzyme Corporation, Framingham, Massachusetts, United States of America
    PLoS ONE 7:e43310. 2012
    ..disease (nGD), also known as type 2 or type 3 Gaucher disease, is caused by a deficiency of the enzyme glucocerebrosidase (GC)...
  52. pmc Substrate compositional variation with tissue/region and Gba1 mutations in mouse models--implications for Gaucher disease
    Ying Sun
    Division of Human Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
    PLoS ONE 8:e57560. 2013
    Gaucher disease results from GBA1 mutations that lead to defective acid β-glucosidase (GCase) mediated cleavage of glucosylceramide (GC) and glucosylsphingosine as well as heterogeneous manifestations in the viscera and CNS...
  53. pmc Gene mapping and leader polypeptide sequence of human glucocerebrosidase: implications for Gaucher disease
    E I Ginns
    Proc Natl Acad Sci U S A 82:7101-5. 1985
    ..Chinese hamster-human somatic cell hybrids allowed assignment of the structural gene for glucocerebrosidase (glucosylceramidase; beta-D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45) to chromosome 1 bands q21-q32...
  54. ncbi Characterization of B61, the ligand for the Eck receptor protein-tyrosine kinase
    H Shao
    Department of Pathology, University of Michigan Medical School, Ann Arbor 48109
    J Biol Chem 270:5636-41. 1995
    ..Finally, the gene for B61 was localized to a specific position on mouse chromosome 3 by interspecific back-cross analysis...
  55. pmc Metaxin, a gene contiguous to both thrombospondin 3 and glucocerebrosidase, is required for embryonic development in the mouse: implications for Gaucher disease
    P Bornstein
    Department of Biochemistry, University of Washington, Seattle 98195, USA
    Proc Natl Acad Sci U S A 92:4547-51. 1995
    We have identified a murine gene, metaxin, that spans the 6-kb interval separating the glucocerebrosidase gene (GC) from the thrombospondin 3 gene on chromosome 3E3-F1...
  56. ncbi Molecular cloning, characterization, and genetic mapping of the cDNA coding for a novel secretory protein of mouse. Demonstration of alternative splicing in skin and cartilage
    J Bhalerao
    Department of Biochemistry, University of Antwerp, Belgium
    J Biol Chem 270:16385-94. 1995
    ..Alternative splicing may serve as a mechanism for generating functional diversity in the Ecm1 gene...
  57. ncbi Long-term expression of the glucocerebrosidase gene in mouse and human hematopoietic progenitors
    M Nimgaonkar
    Department of Medicine, University of Pittsburgh Medical Center, PA, USA
    Leukemia 9:S38-42. 1995
    ..Animal models have demonstrated the feasibility of introducing the human glucocerebrosidase (GC) gene into hematopoietic progenitors with long term expression using a variety of retroviral vectors...
  58. ncbi A lysosomal storage disorder in mice characterized by a dual deficiency of sphingomyelinase and glucocerebrosidase
    P G Pentchev
    Biochim Biophys Acta 619:669-79. 1980
    ..Sphingomyelinase and glucocerebrosidase activities were consistently diminished in a wide variety of tissues obtained from the affected mice...
  59. ncbi Molecular and functional characterization of the murine glucocerebrosidase gene
    E D Carstea
    Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892
    Biochem Biophys Res Commun 184:1477-83. 1992
    A genomic clone of glucocerebrosidase (D-glucosyl-N-acyl-sphingosine glucohydrolase; E.C. 3.2.1...
  60. ncbi Mapping of the mouse 86-kDa heat-shock protein expressed gene (Hsp86-1) on chromosome 12 and related genes on chromosomes 3, 4, 9, and 11
    S K Moore
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892
    Genomics 10:1019-29. 1991
    ..An HSP86-related locus specific to NFS/N and C58/J mice, designated Hsp86-ps3, was mapped on Chromosome 9. Also, an HSP86-related locus that was unique to NFS/N mice, designated Hsp86-ps4, was mapped to Chromosome 4...
  61. ncbi Chromosomal localization of Cd1d genes in the mouse
    A Bradbury
    Instituto di Neurobiologia, Rome, Italy
    Somat Cell Mol Genet 17:93-6. 1991
    ..Analysis of the progeny of an intersubspecies backcross was used to position these genes near the gene for glucocerebrosidase, Gba.
  62. ncbi NSCL-2: a basic domain helix-loop-helix gene expressed in early neurogenesis
    V GOBEL
    Navy Medical Oncology, National Cancer Institute, NIH, Bethesda, Maryland 20892
    Cell Growth Differ 3:143-8. 1992
    ....
  63. ncbi Organization and chromosomal locations of Rap1a/Krev sequences in the mouse
    N A Dower
    Department of Paediatrics, University of Alberta, Edmonton, Canada
    Mamm Genome 3:162-7. 1992
    ..Rap1a-rs2 is more distantly related to the gene sequence and is located on Chr 2 near Actc-1...
  64. ncbi Structure and mapping of the gene encoding mouse high affinity Fc gamma RI and chromosomal location of the human Fc gamma RI gene
    N Osman
    Austin Research Institute, Austin Hospital, Heidelberg, Australia
    J Immunol 148:1570-5. 1992
    ..These results suggest that the linkage relationships among these genes in the human genome are not preserved in the mouse...
  65. ncbi Chromosomal mapping of the high affinity Fc gamma receptor gene
    R J Oakey
    Department of Medicine, Duke University Medical Center, Durham, NC 27710
    Immunogenetics 35:279-82. 1992
  66. ncbi High throughput quantitative glycomics and glycoform-focused proteomics of murine dermis and epidermis
    Rie Uematsu
    Division of Biological Sciences, Graduate School of Science, Frontier Research Center for Post Genomic Science and Technology, Hokkaido University, Sapporo 001 0021, Japan
    Mol Cell Proteomics 4:1977-89. 2005
    ..g. cathepsin L and gamma-glutamyl hydrolase), lamellar granules (e.g. glucosylceramidase and cathepsin D), and desmosomes (e.g. desmocollin 1, desmocollin 3, and desmoglein)...
  67. pmc Animal models for Gaucher disease research
    Tamar Farfel-Becker
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Dis Model Mech 4:746-52. 2011
    ..most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene...
  68. ncbi LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase
    David Reczek
    Genzyme Corporation, 1 Mountain Road, Framingham, MA 01701, USA
    Cell 131:770-83. 2007
    beta-glucocerebrosidase, the enzyme defective in Gaucher disease, is targeted to the lysosome independently of the mannose-6-phosphate receptor...
  69. ncbi A physical map of the genomic region on mouse chromosome 3 containing the hindshaker (hsh) mutation
    Saadia A Karim
    Applied Neurobiology Group, Institute of Comparative Medicine, Veterinary School, United Kingdom
    Genomics 83:225-30. 2004
    ..Accordingly, our findings both map the area surrounding the hsh mutation and present important corrections to the current maps in an area rich in genes related to the nervous system...
  70. ncbi Role of peroxisome proliferator-activated receptor alpha in epidermal development in utero
    Matthias Schmuth
    Departments of Medicine Dermatology, University of California San Francisco, California 94121, USA
    J Invest Dermatol 119:1298-303. 2002
    ..5 of gestation and birth. Concurrently, there was diminished beta-glucocerebrosidase activity at the stratum granulosum-stratum corneum junction and a modest decrease in both involucrin and ..
  71. ncbi Temporal and spatial expression of murine acid beta-glucosidase mRNA
    E Ponce
    Division of Human Genetics, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    Mol Genet Metab 74:426-34. 2001
    ..glucosylceramide (GC) to ceramide and glucose requires the action of the lysosomal enzyme, acid beta-glucosidase (GCase), encoded by gba in the mouse...
  72. ncbi Comparative analysis of the human and mouse Hey1 promoter: Hey genes are new Notch target genes
    M M Maier
    Physiologische Chemie I, Biozentrum der Universität Würzburg, Am Hubland, Wurzburg, 97074, Germany
    Biochem Biophys Res Commun 275:652-60. 2000
    ..Thus, our data clearly demonstrate that Hey genes form a new class of Notch signal transducers that should prove to be relevant in various developmental processes...
  73. pmc A comparative gene map of the horse (Equus caballus)
    A R Caetano
    Veterinary Genetics Laboratory, University of California Davis, Davis, California 95616 8744, USA
    Genome Res 9:1239-49. 1999
    ..The equine type I markers developed in this study provide an important resource for the future development of the horse linkage and physical genome maps...
  74. ncbi Mouse annexin V chromosomal localization, cDNA sequence conservation, and molecular evolution
    M I Rodriguez-Garcia
    Department of Biochemistry and Molecular Biology, University of Oviedo, Spain
    Genomics 31:151-7. 1996
    ..Comparison of nine species of ANX5 led to an estimation of the unit evolutionary mutation rate at 1% aa replacements every 8 million years, comparable to other annexins...
  75. ncbi cDNA cloning, sequencing and chromosomal assignment of the gene for mouse complement factor I (C3b/C4b inactivator): identification of a species specific divergent segment in factor I
    J O Minta
    Department of Cellular and Molecular Pathology, University of Toronto, Canada
    Mol Immunol 33:101-12. 1996
    ..The significance of the diversity of the D segment is at present unclear. We also report the chromosomal localization of the mouse factor I gene (Cfi) to distal chromosome 3 near Egf...
  76. ncbi A tightly organized, conserved gene cluster on mouse chromosome 3 (E3-F1)
    H L Vos
    Department of Tumor Biology, Netherlands Cancer Institute, Amsterdam, The Netherlands
    Mamm Genome 6:820-2. 1995
  77. ncbi The genes encoding gonadal and nongonadal forms of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase are closely linked on mouse chromosome 3
    P A Bain
    Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor 48109
    Genomics 16:219-23. 1993
    ..The order of markers on Chr 3 surrounding Hsd3b is: centromere-Gba-(4.4 +/- 2.2)-Hsd3b-(3.3 +/- 1.9)-Tshb-(6.7 +/- 2.7)-Amy-1.
  78. ncbi Coexpression of gap junction proteins in the cumulus-oocyte complex
    G Valdimarsson
    Department of Zoology, University of Western Ontario, London, Canada
    Mol Reprod Dev 36:7-15. 1993
    ..We could find no evidence of the incorporation of the oocyte's store of Cx32 into gap junctions during postfertilization development.(ABSTRACT TRUNCATED AT 250 WORDS)..
  79. ncbi Corticotropin-releasing hormone (Crh) maps to mouse chromosome 3
    L T Knapp
    Department of Human Genetics, University of Michigan Medical School, Ann Arbor 48109 1618
    Mamm Genome 4:615-7. 1993
  80. ncbi Permeability barrier requirements regulate epidermal beta-glucocerebrosidase
    W M Holleran
    Department of Dermatology, University of California School of Medicine, San Francisco
    J Lipid Res 35:905-12. 1994
    ..Hence, hydrolysis of GlcCer to Cer by beta-glucocerebrosidase (GlcCer'ase), may be required for permeability barrier homeostasis...
  81. ncbi Genetic mapping of the gene encoding guanylate cyclase-A/atrial natriuretic factor receptor (Npra) to mouse chromosome 3
    K N Pandey
    Department of Biochemistry and Molecular Biology, Medical College of Georgia, School of Medicine, Augusta 30912 2100
    Mamm Genome 5:520-2. 1994
  82. ncbi Localization of the osteocalcin gene cluster on mouse chromosome 3
    C Desbois
    Department of Molecular Genetics, University of Texas, M D Anderson Cancer Center, Houston 77030
    Mamm Genome 5:321-2. 1994
  83. ncbi Biosynthesis of acylceramide in murine epidermis: characterization by inhibition of glucosylation and deglucosylation, and by substrate specificity
    Yutaka Takagi
    Department of Dermatology, Jichi Medical University, Tochigi, Japan
    J Invest Dermatol 122:722-9. 2004
    ..When conduritol-B-epoxide, a specific inhibitor of beta-glucocerebrosidase, was added to the culture medium, the synthesis of acylceramide was significantly suppressed in concert with ..

Research Grants3

  1. INBORN ERRORS OF SPHINGOLIPID CATABOLISM
    Gregory Grabowski; Fiscal Year: 2004
    ..abstract_text> ..
  2. Use of Hammerhead Ribozymes in Murine Models of Ol
    Gregory Grabowski; Fiscal Year: 2007
    ....
  3. Studies of Prosaposin's Physiologic Role
    Gregory Grabowski; Fiscal Year: 2007
    ..These studies have implications for GSL metabolism, and lysosomal storage disease phenotypic expression and therapy. ..