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
Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1α
Aimee Y. Yu, … , J.T. Sylvester, Gregg L. Semenza
Aimee Y. Yu, … , J.T. Sylvester, Gregg L. Semenza
Published March 1, 1999
Citation Information: J Clin Invest. 1999;103(5):691-696. https://doi.org/10.1172/JCI5912.
View: Text | PDF
Article Article has an altmetric score of 3

Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1α

  • Text
  • PDF
Abstract

Chronic hypoxia induces polycythemia, pulmonary hypertension, right ventricular hypertrophy, and weight loss. Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding proteins that mediate adaptive responses to hypoxia, including erythropoietin, vascular endothelial growth factor, and glycolytic enzymes. Expression of the HIF-1α subunit increases exponentially as O2 concentration is decreased. Hif1a–/– mouse embryos with complete deficiency of HIF-1α due to homozygosity for a null allele at the Hif1a locus die at midgestation, with multiple cardiovascular malformations and mesenchymal cell death. Hif1a+/– heterozygotes develop normally and are indistinguishable from Hif1a+/+ wild-type littermates when maintained under normoxic conditions. In this study, the physiological responses of Hif1a+/– and Hif1a+/+ mice exposed to 10% O2 for one to six weeks were analyzed. Hif1a+/– mice demonstrated significantly delayed development of polycythemia, right ventricular hypertrophy, pulmonary hypertension, and pulmonary vascular remodeling and significantly greater weight loss compared with wild-type littermates. These results indicate that partial HIF-1α deficiency has significant effects on multiple systemic responses to chronic hypoxia.

Authors

Aimee Y. Yu, Larissa A. Shimoda, Narayan V. Iyer, David L. Huso, Xing Sun, Rita McWilliams, Terri Beaty, James S.K. Sham, Charles M. Wiener, J.T. Sylvester, Gregg L. Semenza

×

Full Text PDF

Download PDF (307.58 KB)

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

Sign up for email alerts

Referenced in 3 patents
196 readers on Mendeley
See more details