Polycythemia in transgenic mice expressing the human erythropoietin gene.
PDF (1.5M)
Journal: 1989/May - Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
PUBMED: 2928334
Abstract:
Erythropoietin is a glycoprotein hormone that regulates mammalian erythropoiesis. To study the expression of the human erythropoietin gene, EPO, 4 kilobases of DNA encompassing the gene with 0.4 kilobase of 5' flanking sequence and 0.7 kilobase of 3' flanking sequence was microinjected into fertilized mouse eggs. Transgenic mice were generated that are polycythemic, with increased erythrocytic indices in peripheral blood, increased numbers of erythroid precursors in hematopoietic tissue, and increased serum erythropoietin levels. Transgenic homozygotes show a greater degree of polycythemia than do heterozygotes as well as striking extramedullary erythropoiesis. Human erythropoietin RNA was found not only in fetal liver, adult liver, and kidney but also in all other transgenic tissues analyzed. Anemia induced increased human erythropoietin RNA levels in liver but not kidney. These transgenic mice represent a unique model of polycythemia due to increased erythropoietin levels.
Open in
PUBMED | PMC | Google Scholar | Wikipedia
Relations:
Content
Citations
(36)
References
(24)
Diseases
(1)
Chemicals
(1)
Organisms
(5)
Processes
(4)
Affiliates
(2)
Similar articles
Articles by the same authors
Discussion board
Proc Natl Acad Sci U S A 86(7): 2301-2305
PMID: 2928334

Polycythemia in transgenic mice expressing the human erythropoietin gene.

Abstract

Erythropoietin is a glycoprotein hormone that regulates mammalian erythropoiesis. To study the expression of the human erythropoietin gene, EPO, 4 kilobases of DNA encompassing the gene with 0.4 kilobase of 5' flanking sequence and 0.7 kilobase of 3' flanking sequence was microinjected into fertilized mouse eggs. Transgenic mice were generated that are polycythemic, with increased erythrocytic indices in peripheral blood, increased numbers of erythroid precursors in hematopoietic tissue, and increased serum erythropoietin levels. Transgenic homozygotes show a greater degree of polycythemia than do heterozygotes as well as striking extramedullary erythropoiesis. Human erythropoietin RNA was found not only in fetal liver, adult liver, and kidney but also in all other transgenic tissues analyzed. Anemia induced increased human erythropoietin RNA levels in liver but not kidney. These transgenic mice represent a unique model of polycythemia due to increased erythropoietin levels.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
icon of scanned page 2301
2301
icon of scanned page 2302
2302
icon of scanned page 2303
2303
icon of scanned page 2304
2304
icon of scanned page 2305
2305

Images in this article

Image
Image
on p.2302
Image
Image
on p.2302
Image
Image
on p.2304
Image
Image
on p.2304
Image
Image
on p.2304
Image
Image
on p.2304
Image
Image
on p.2304
Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Jelkmann W. Renal erythropoietin: properties and production. Rev Physiol Biochem Pharmacol. 1986;104:139–215. [PubMed] [Google Scholar]
  • JACOBSON LO, GOLDWASSER E, FRIED W, PLZAK L. Role of the kidney in erythropoiesis. Nature. 1957 Mar 23;179(4560):633–634. [PubMed] [Google Scholar]
  • Beru N, McDonald J, Lacombe C, Goldwasser E. Expression of the erythropoietin gene. Mol Cell Biol. 1986 Jul;6(7):2571–2575.[PMC free article] [PubMed] [Google Scholar]
  • Koury ST, Bondurant MC, Koury MJ. Localization of erythropoietin synthesizing cells in murine kidneys by in situ hybridization. Blood. 1988 Feb;71(2):524–527. [PubMed] [Google Scholar]
  • Bondurant MC, Koury MJ. Anemia induces accumulation of erythropoietin mRNA in the kidney and liver. Mol Cell Biol. 1986 Jul;6(7):2731–2733.[PMC free article] [PubMed] [Google Scholar]
  • Zanjani ED, Poster J, Burlington H, Mann LI, Wasserman LR. Liver as the primary site of erythropoietin formation in the fetus. J Lab Clin Med. 1977 Mar;89(3):640–644. [PubMed] [Google Scholar]
  • Koury MJ, Bondurant MC, Graber SE, Sawyer ST. Erythropoietin messenger RNA levels in developing mice and transfer of 125I-erythropoietin by the placenta. J Clin Invest. 1988 Jul;82(1):154–159.[PMC free article] [PubMed] [Google Scholar]
  • Schuster SJ, Wilson JH, Erslev AJ, Caro J. Physiologic regulation and tissue localization of renal erythropoietin messenger RNA. Blood. 1987 Jul;70(1):316–318. [PubMed] [Google Scholar]
  • Goldberg MA, Glass GA, Cunningham JM, Bunn HF. The regulated expression of erythropoietin by two human hepatoma cell lines. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7972–7976.[PMC free article] [PubMed] [Google Scholar]
  • Jacobs K, Shoemaker C, Rudersdorf R, Neill SD, Kaufman RJ, Mufson A, Seehra J, Jones SS, Hewick R, Fritsch EF, et al. Isolation and characterization of genomic and cDNA clones of human erythropoietin. Nature. 313(6005):806–810. [PubMed] [Google Scholar]
  • Lin FK, Suggs S, Lin CH, Browne JK, Smalling R, Egrie JC, Chen KK, Fox GM, Martin F, Stabinsky Z, et al. Cloning and expression of the human erythropoietin gene. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7580–7584.[PMC free article] [PubMed] [Google Scholar]
  • Shoemaker CB, Mitsock LD. Murine erythropoietin gene: cloning, expression, and human gene homology. Mol Cell Biol. 1986 Mar;6(3):849–858.[PMC free article] [PubMed] [Google Scholar]
  • McDonald JD, Lin FK, Goldwasser E. Cloning, sequencing, and evolutionary analysis of the mouse erythropoietin gene. Mol Cell Biol. 1986 Mar;6(3):842–848.[PMC free article] [PubMed] [Google Scholar]
  • Brinster RL, Chen HY, Trumbauer ME, Yagle MK, Palmiter RD. Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4438–4442.[PMC free article] [PubMed] [Google Scholar]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed] [Google Scholar]
  • Semenza GL, Ladias JA, Antonarakis SE. An Xba I polymorphism 3' to the human erythropoietin (EPO) gene. Nucleic Acids Res. 1987 Aug 25;15(16):6768–6768.[PMC free article] [PubMed] [Google Scholar]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed] [Google Scholar]
  • O'Hara BF, Bendotti C, Reeves RH, Oster-Granite ML, Coyle JT, Gearhart JD. Genetic mapping and analysis of somatostatin expression in Snell dwarf mice. Brain Res. 1988 Dec;464(4):283–292. [PubMed] [Google Scholar]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed] [Google Scholar]
  • Thomas PS. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205.[PMC free article] [PubMed] [Google Scholar]
  • Hanukoglu I, Tanese N, Fuchs E. Complementary DNA sequence of a human cytoplasmic actin. Interspecies divergence of 3' non-coding regions. J Mol Biol. 1983 Feb 5;163(4):673–678. [PubMed] [Google Scholar]
  • Egrie JC, Cotes PM, Lane J, Gaines Das RE, Tam RC. Development of radioimmunoassays for human erythropoietin using recombinant erythropoietin as tracer and immunogen. J Immunol Methods. 1987 May 20;99(2):235–241. [PubMed] [Google Scholar]
  • Danesino C, Gimelli G, Cuoco C, Ciccone MO. Triplex gene dosage effect of beta-glucuronidase and possible assignment to band q22 in a partial duplication 7q. Hum Genet. 1981;56(3):371–373. [PubMed] [Google Scholar]
  • Law ML, Cai GY, Lin FK, Wei Q, Huang SZ, Hartz JH, Morse H, Lin CH, Jones C, Kao FT. Chromosomal assignment of the human erythropoietin gene and its DNA polymorphism. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6920–6924.[PMC free article] [PubMed] [Google Scholar]
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Copyright notice
Abstract
Erythropoietin is a glycoprotein hormone that regulates mammalian erythropoiesis. To study the expression of the human erythropoietin gene, EPO, 4 kilobases of DNA encompassing the gene with 0.4 kilobase of 5' flanking sequence and 0.7 kilobase of 3' flanking sequence was microinjected into fertilized mouse eggs. Transgenic mice were generated that are polycythemic, with increased erythrocytic indices in peripheral blood, increased numbers of erythroid precursors in hematopoietic tissue, and increased serum erythropoietin levels. Transgenic homozygotes show a greater degree of polycythemia than do heterozygotes as well as striking extramedullary erythropoiesis. Human erythropoietin RNA was found not only in fetal liver, adult liver, and kidney but also in all other transgenic tissues analyzed. Anemia induced increased human erythropoietin RNA levels in liver but not kidney. These transgenic mice represent a unique model of polycythemia due to increased erythropoietin levels.
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.