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Renal Anemia Model Mouse Established by Transgenic Rescue with an Erythropoietin Gene Lacking Kidney-Specific Regulatory Elements
- Source :
- Molecular and Cellular Biology. 37
- Publication Year :
- 2017
- Publisher :
- Informa UK Limited, 2017.
-
Abstract
- The erythropoietin (Epo) gene is under tissue-specific inducible regulation. Because the kidney is the primary EPO-producing tissue in adults, impaired EPO production in chronic kidney disorders results in serious renal anemia. The Epo gene contains a liver-specific enhancer in the 3′ region, but the kidney-specific enhancer for gene expression in renal EPO-producing (REP) cells remains elusive. Here, we examined a conserved upstream element for renal Epo regulation (CURE) region that spans 17.4 kb to 3.6 kb upstream of the Epo gene and harbors several phylogenetically conserved elements. We prepared various Epo gene-reporter constructs utilizing a bacterial artificial chromosome and generated a number of transgenic-mouse lines. We observed that deletion of the CURE region (δCURE) abrogated Epo gene expression in REP cells. Although transgenic expression of the δCURE construct rescued Epo-deficient mice from embryonic lethality, the rescued mice had severe EPO-dependent anemia. These mouse lines serve as an elaborate model for the search for erythroid stimulatory activity and are referred to as AnRED (anemic model with renal EPO deficiency) mice. We also dissected the CURE region by exploiting a minigene harboring four phylogenetically conserved elements in reporter transgenic-mouse analyses. Our analyses revealed that Epo gene regulation in REP cells is a complex process that utilizes multiple regulatory influences.
- Subjects :
- Male
0301 basic medicine
Genotype
Transgene
Green Fluorescent Proteins
Mice, Transgenic
Polycythemia
Biology
Kidney
Response Elements
Models, Biological
03 medical and health sciences
Fetus
hemic and lymphatic diseases
Gene expression
medicine
Animals
Homeostasis
Transgenes
Enhancer
Base Pairing
Erythropoietin
Molecular Biology
Conserved Sequence
Crosses, Genetic
Sequence Deletion
Regulation of gene expression
Genetics
Brain
Anemia
Cell Biology
Molecular biology
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Organ Specificity
Embryo Loss
Female
Kidney disorder
Research Article
Minigene
medicine.drug
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biology
- Accession number :
- edsair.doi.dedup.....682ec714336fea8108d1253910b43542