Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease.
W M Holleran, … , P M Elias, E Sidransky
W M Holleran, … , P M Elias, E Sidransky
Published April 1, 1994
Citation Information: J Clin Invest. 1994;93(4):1756-1764. https://doi.org/10.1172/JCI117160.
View: Text | PDF
Research Article Article has an altmetric score of 3

Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease.

  • Text
  • PDF
Abstract

Hydrolysis of glucosylceramide by beta-glucocerebrosidase results in ceramide, a critical component of the intercellular lamellae that mediate the epidermal permeability barrier. A subset of type 2 Gaucher patients displays ichthyosiform skin abnormalities, as do transgenic Gaucher mice homozygous for a null allele. To investigate the relationship between glucocerebrosidase deficiency and epidermal permeability barrier function, we compared the stratum corneum (SC) ultrastructure, lipid content, and barrier function of Gaucher mice to carrier and normal mice, and to hairless mice treated topically with bromoconduritol B epoxide (BrCBE), an irreversible inhibitor of glucocerebrosidase. Both Gaucher mice and BrCBE-treated mice revealed abnormal, incompletely processed, lamellar body-derived sheets throughout the SC interstices, while transgenic carrier mice displayed normal bilayers. The SC of a severely affected type 2 Gaucher's disease infant revealed similarly abnormal ultrastructure. Furthermore, the Gaucher mice demonstrated markedly elevated transepidermal water loss (4.2 +/- 0.6 vs < 0.10 g/m2 per h). The electron-dense tracer, colloidal lanthanum, percolated between the incompletely processed lamellar body-derived sheets in the SC interstices of Gaucher mice only, demonstrating altered permeability barrier function. Gaucher and BrCBE-treated mice showed < 1% and < 5% of normal epidermal glucocerebrosidase activity, respectively, and the epidermis/SC of Gaucher mice demonstrated elevated glucosylceramide (5- to 10-fold), with diminished ceramide content. Thus, the skin changes observed in Gaucher mice and infants may result from the formation of incompetent intercellular lamellar bilayers due to a decreased hydrolysis of glucosylceramide to ceramide. Glucocerebrosidase therefore appears necessary for the generation of membranes of sufficient functional competence for epidermal barrier function.

Authors

W M Holleran, E I Ginns, G K Menon, J U Grundmann, M Fartasch, C E McKinney, P M Elias, E Sidransky

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1992 Total
Citations: 2 6 1 4 10 5 4 7 11 10 7 9 18 13 6 6 5 11 6 9 14 4 8 9 2 8 11 10 7 9 8 1 1 242
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2015 (7)

Title and authors Publication Year
Dissecting the formation, structure and barrier function of the stratum corneum
T Matsui, M Amagai
International Immunology 2015
The clinical management of type 2 Gaucher disease
K Weiss, AN Gonzalez, G Lopez, L Pedoeim, C Groden, E Sidransky
Molecular Genetics and Metabolism 2015
Viable Neuronopathic Gaucher Disease Model in Medaka (Oryzias latipes) Displays Axonal Accumulation of Alpha-Synuclein
N Uemura, M Koike, S Ansai, M Kinoshita, T Ishikawa-Fujiwara, H Matsui, K Naruse, N Sakamoto, Y Uchiyama, T Todo, S Takeda, H Yamakado, R Takahashi, B Lu
PLoS genetics 2015
Molecular studies on parents after autopsy identify recombinant GBA gene in a case of Gaucher disease with ichthyosis phenotype
S Aggarwal, SJ Jain, AD Bhowmik, A Tandon, A Dalal
American Journal of Medical Genetics Part A 2015
Hyaluronan tetrasaccharides stimulate ceramide production through upregulated mRNA expression of ceramide synthesis-associated enzymes
M Kage, Y Tokudome
Archives of Dermatological Research 2015
The (Mostly) Good, the (Few) Bad, and the (Couple of) Ugly Chapters in Sturkie’s Avian Physiology Sturkie’s Avian Physiology . Edited by Colin G. Scanes . Waltham, MA: Academic Press, 2014. ISBN 978-0-124-07160-5
JB Williams
Physiological and Biochemical Zoology 2015
Lipid composition and molecular interactions change with depth in the avian stratum corneum to regulate cutaneous water loss
AM Champagne, HC Allen, JB Williams
The Journal of experimental biology 2015

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 3 patents
60 readers on Mendeley
See more details