Cell-type-specific and hypoxia-inducible expression of the human erythropoietin gene in transgenic mice

G. L. Semenza, S. T. Koury, M. K. Nejfelt, J. D. Gearhart, S. E. Antonarakis

Research output: Contribution to journalArticle

Abstract

Synthesis of erythropoietin, the primary humoral regulator of erythropoiesis, in liver and kidney is inducible by anemia or hypoxia. Analysis of human erythropoietin gene expression in transgenic mice revealed that sequences located 6-14 kilobases 5' to the gene direct expression to the kidney, whereas sequences within the immediate 3'-flanking region control hepatocyte-specific expression. Human erythropoietin transcription initiation sites were differentially utilized in liver and kidney. Inducible transgene expression was precisely targeted to peritubular interstitial cells in the renal cortex that synthesize endogenous mouse erythropoietin. These studies demonstrate that multiple erythropoietin gene regulatory elements control cell-type-specific expression and inducibility by a fundamental physiologic stimulus, hypoxia.

Original languageEnglish (US)
Pages (from-to)8725-8729
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number19
DOIs
StatePublished - Oct 24 1991

Keywords

  • enhancer elements
  • gene regulation
  • in situ hybridization
  • polycythemia

ASJC Scopus subject areas

  • General

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