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), Vol. 88:19; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

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