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

Journal Article · Tue Oct 01 00:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.19.8725· OSTI ID:5604494

Semenza, G L; Nejfelt, M K; Gearhart, J D; Antonarakis, S E ^[1]; Koury, S T ^[2]

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1. Johns Hopkins Univ., Baltimore, MD (United States)
2. Vanderbilt Univ., Nashville, TN (United States)

Synthesis of erythropoietin, the primary humoral regulator or 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{prime} to the gene direct expression to the kidney, whereas sequences within the immediate 3{prime}-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 cello-type-specific expression and inducibility by a fundamental physiologic stimulus, hypoxia.

• OSTI ID: 5604494
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:19; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANEMIAS
ANIMALS
ANOXIA
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BLOOD FORMATION
BODY
CHEMICAL ACTIVATION
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
DNA HYBRIDIZATION
ERYTHROPOIESIS
ERYTHROPOIETIN
EVEN-ODD NUCLEI
GENE REGULATION
GLANDS
HEMIC DISEASES
HORMONES
HYBRIDIZATION
ISOTOPES
KIDNEYS
LIGHT NUCLEI
LIVER
MAMMALS
MESSENGER-RNA
MICE
MITOGENS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PROTEINS
RADIOISOTOPES
RNA
RODENTS
SULFUR 35
SULFUR ISOTOPES
SYMPTOMS
TRANSCRIPTION
VERTEBRATES