Evidence map›Paper›PMID 27482815›Full record

ArticleDisease models & mechanisms2016

A new glucocerebrosidase-deficient neuronal cell model provides a tool to probe pathophysiology and therapeutics for Gaucher disease.

Wendy Westbroek, Matthew Nguyen, Marina Siebert, Taylor Lindstrom, Robert A Burnett, Elma Aflaki, Olive Jung, Rafael Tamargo, Jorge L Rodriguez-Gil, Walter Acosta and 13 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Disease models & mechanisms, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. iPSC-derived neural precursor cells engineeringMolecular therapy. Methods & clinical development · 2023
    Article
  5. Article
  6. PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects,Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  7. Live cellFrontiers in cellular neuroscience · 2023
    Article
  8. Article
  9. Neuronopathic Gaucher disease: Beyond lysosomal dysfunction.Frontiers in molecular neuroscience · 2022
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Acidic CaMessenger (Los Angeles, Calif. : Print) · 2016
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 6 institutions in 3 countries.

Wendy WestbroekSection on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Matthew NguyenSection on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Marina SiebertSection on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA Postgraduate Program in Cellular and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 91501-970, Brazil.
Taylor LindstromSection on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Robert A BurnettSection on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Elma AflakiSection on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Olive JungSection on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Rafael TamargoSection on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jorge L Rodriguez-GilGenomics, Development, and Disease Section, Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Walter AcostaBiostrategies LC, State University, AR 72467, USA.
An HendrixLaboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent 9000, Belgium.
Bahafta BehreSection on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nahid TayebiSection on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Hideji FujiwaraWashington University School of Medicine, St. Louis, MO 63110-1093, USA.
Rohini SidhuWashington University School of Medicine, St. Louis, MO 63110-1093, USA.
Benoit RenvoiseCell Biology Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Edward I GinnsLysosomal Disorders Treatment and Research Program, Clinical Labs, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Amalia DutraCytogenetics Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Evgenia PakCytogenetics Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Carole CramerBiostrategies LC, State University, AR 72467, USA.
Daniel S OryWashington University School of Medicine, St. Louis, MO 63110-1093, USA.
William J PavanGenomics, Development, and Disease Section, Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ellen SidranskySection on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA sidranse@mail.nih.gov.ORCID 0000-0002-3019-8500
National Institutes of Health · USWashington University in St. Louis · USBioStrategies (United States) · USNational Human Genome Research Institute · USGhent University Hospital · BEUniversity of Massachusetts Chan Medical School · US

Funding

Genetic and clinical studies of Gaucher disease and other lysosomal disordersZIAHG200336 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI SIDRANSKY, ELLEN · 2009 to 2025
$45.2M
WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1M
INTEGRATED TRAINING FOR PHYSICIAN-SCIENTISTST32GM008692 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BURKARD, MARK E · 1998 to 2020
$10.3M
THE USE OF THE MOUSE NPC MODEL TO CLONE THE HUMAN DISEASE GENEZIAHG000068 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI PAVAN, WILLIAM J · 2009 to 2023
$6.0M
Improving MPS I ERT Efficacy through Lectin-Mediated DeliveryR43NS086326 · NINDS · BIOSTRATEGIES, LC · PI CRAMER, CAROLE L., RADIN, DAVID · 2014 to 2015
$644k
NIDDK NIH HHS P30 DK020579NIGMS NIH HHS T32 GM008692NINDS NIH HHS R43 NS086326
6 · The paper itself

Abstract

Glucocerebrosidase is a lysosomal hydrolase involved in the breakdown of glucosylceramide. Gaucher disease, a recessive lysosomal storage disorder, is caused by mutations in the gene GBA1 Dysfunctional glucocerebrosidase leads to accumulation of glucosylceramide and glycosylsphingosine in various cell types and organs. Mutations in GBA1 are also a common genetic risk factor for Parkinson disease and related synucleinopathies. In recent years, research on the pathophysiology of Gaucher disease, the molecular link between Gaucher and Parkinson disease, and novel therapeutics, have accelerated the need for relevant cell models with GBA1 mutations. Although induced pluripotent stem cells, primary rodent neurons, and transfected neuroblastoma cell lines have been used to study the effect of glucocerebrosidase deficiency on neuronal function, these models have limitations because of challenges in culturing and propagating the cells, low yield, and the introduction of exogenous mutant GBA1 To address some of these difficulties, we established a high yield, easy-to-culture mouse neuronal cell model with nearly complete glucocerebrosidase deficiency representative of Gaucher disease. We successfully immortalized cortical neurons from embryonic null allele gba(-/-) mice and the control littermate (gba(+/+)) by infecting differentiated primary cortical neurons in culture with an EF1α-SV40T lentivirus. Immortalized gba(-/-) neurons lack glucocerebrosidase protein and enzyme activity, and exhibit a dramatic increase in glucosylceramide and glucosylsphingosine accumulation, enlarged lysosomes, and an impaired ATP-dependent calcium-influx response; these phenotypical characteristics were absent in gba(+/+) neurons. This null allele gba(-/-) mouse neuronal model provides a much-needed tool to study the pathophysiology of Gaucher disease and to evaluate new therapies.

Indexed as

Models, BiologicalAdenosine TriphosphateAnimalsAntigens, Polyomavirus TransformingCalciumCD24 AntigenCell Line, TransformedCells, CulturedGaucher DiseaseGlucosylceramidaseKaryotypingLysosomesMice, Inbred C57BLNeuronsPeptide Elongation Factor 1Promoter Regions, GeneticAdenosine TriphosphateAntigens, Polyomavirus TransformingCalciumCD24 AntigenGlucosylceramidasePeptide Elongation Factor 1Gaucher diseaseGlucocerebrosidaseGlucosylceramideGlucosylsphingosineNeuron

Identifiers

PMID27482815
PMCPMC4958308
OpenAlexW2405127594

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.