Open AccessCell-type-specific and hypoxia-inducible expression of the human erythropoietin gene in transgenic mice.
Author(s) -
Gregg L. Semenza,
Stephen T. Koury,
Mary K. Nejfelt,
John D. Gearhart,
Stylianos E. Antonarakis
Publication year - 1991
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.88.19.8725
Subject(s) - erythropoietin , erythropoiesis , biology , transgene , gene expression , genetically modified mouse , kidney , gene , transcription factor , hypoxia inducible factors , microbiology and biotechnology , hypoxia (environmental) , endocrinology , medicine , anemia , genetics , chemistry , organic chemistry , oxygen
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.