Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • 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
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI3729

Dysregulated hematopoiesis and a progressive neurological disorder induced by expression of an activated form of the human common beta chain in transgenic mice.

R J D'Andrea, D Harrison-Findik, C M Butcher, J Finnie, P Blumbergs, P Bartley, M McCormack, K Jones, R Rowland, T J Gonda, and M A Vadas

The Hanson Centre for Cancer Research, Division of Human Immunology, Adelaide, 5000 South Australia, Australia. Richard.Dandrea@imvs.sa

Find articles by D'Andrea, R. in: JCI | PubMed | Google Scholar

The Hanson Centre for Cancer Research, Division of Human Immunology, Adelaide, 5000 South Australia, Australia. Richard.Dandrea@imvs.sa

Find articles by Harrison-Findik, D. in: JCI | PubMed | Google Scholar

The Hanson Centre for Cancer Research, Division of Human Immunology, Adelaide, 5000 South Australia, Australia. Richard.Dandrea@imvs.sa

Find articles by Butcher, C. in: JCI | PubMed | Google Scholar

The Hanson Centre for Cancer Research, Division of Human Immunology, Adelaide, 5000 South Australia, Australia. Richard.Dandrea@imvs.sa

Find articles by Finnie, J. in: JCI | PubMed | Google Scholar

The Hanson Centre for Cancer Research, Division of Human Immunology, Adelaide, 5000 South Australia, Australia. Richard.Dandrea@imvs.sa

Find articles by Blumbergs, P. in: JCI | PubMed | Google Scholar

The Hanson Centre for Cancer Research, Division of Human Immunology, Adelaide, 5000 South Australia, Australia. Richard.Dandrea@imvs.sa

Find articles by Bartley, P. in: JCI | PubMed | Google Scholar

The Hanson Centre for Cancer Research, Division of Human Immunology, Adelaide, 5000 South Australia, Australia. Richard.Dandrea@imvs.sa

Find articles by McCormack, M. in: JCI | PubMed | Google Scholar

The Hanson Centre for Cancer Research, Division of Human Immunology, Adelaide, 5000 South Australia, Australia. Richard.Dandrea@imvs.sa

Find articles by Jones, K. in: JCI | PubMed | Google Scholar

The Hanson Centre for Cancer Research, Division of Human Immunology, Adelaide, 5000 South Australia, Australia. Richard.Dandrea@imvs.sa

Find articles by Rowland, R. in: JCI | PubMed | Google Scholar

The Hanson Centre for Cancer Research, Division of Human Immunology, Adelaide, 5000 South Australia, Australia. Richard.Dandrea@imvs.sa

Find articles by Gonda, T. in: JCI | PubMed | Google Scholar

The Hanson Centre for Cancer Research, Division of Human Immunology, Adelaide, 5000 South Australia, Australia. Richard.Dandrea@imvs.sa

Find articles by Vadas, M. in: JCI | PubMed | Google Scholar

Published December 1, 1998 - More info

Published in Volume 102, Issue 11 on December 1, 1998
J Clin Invest. 1998;102(11):1951–1960. https://doi.org/10.1172/JCI3729.
© 1998 The American Society for Clinical Investigation
Published December 1, 1998 - Version history
View PDF
Abstract

Previously we described activating mutations of hbetac, the common signaling subunit of the receptors for the hematopoietic and inflammatory cytokines, GM-CSF, IL-3, and IL-5. The activated mutant, hbetacFIDelta, is able to confer growth factor-independent proliferation on the murine myeloid cell line FDC-P1, and on primary committed myeloid progenitors. We have used this activating mutation to study the effects of chronic cytokine receptor stimulation. Transgenic mice were produced carrying the hbetacFIDelta cDNA linked to the constitutive promoter derived from the phosphoglycerate kinase gene, PGK-1. Transgene expression was demonstrated in several tissues and functional activity of the mutant receptor was confirmed in hematopoietic tissues by the presence of granulocyte macrophage and macrophage colony-forming cells (CFU-GM and CFU-M) in the absence of added cytokines. All transgenic mice display a myeloproliferative disorder characterized by splenomegaly, erythrocytosis, and granulocytic and megakaryocytic hyperplasia. This disorder resembles the human disease polycythemia vera, suggesting that activating mutations in hbetac may play a role in the pathogenesis of this myeloproliferative disorder. In addition, these transgenic mice develop a sporadic, progressive neurological disease and display bilateral, symmetrical foci of necrosis in the white matter of brain stem associated with an accumulation of macrophages. Thus, chronic hbetac activation has the potential to contribute to pathological events in the central nervous system.

Version history
  • Version 1 (December 1, 1998): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts