In vivo regulation of erythropoiesis by chemically inducible dimerization of the erythropoietin receptor intracellular domain

PloS One
Norio SuzukiMasayuki Yamamoto

Abstract

Erythropoietin (Epo) and its receptor (EpoR) are required for the regulation of erythropoiesis. Epo binds to the EpoR homodimer on the surface of erythroid progenitors and erythroblasts, and positions the intracellular domains of the homodimer to be in close proximity with each other. This conformational change is sufficient for the initiation of Epo-EpoR signal transduction. Here, we established a system of chemically regulated erythropoiesis in transgenic mice expressing a modified EpoR intracellular domain (amino acids 247-406) in which dimerization is induced using a specific compound (chemical inducer of dimerization, CID). Erythropoiesis is reversibly induced by oral administration of the CID to the transgenic mice. Because transgene expression is limited to hematopoietic cells by the Gata1 gene regulatory region, the effect of the CID is limited to erythropoiesis without adverse effects. Additionally, we show that the 160 amino acid sequence is the minimal essential domain of EpoR for intracellular signaling of chemically inducible erythropoiesis in vivo. We propose that the CID-dependent dimerization system combined with the EpoR intracellular domain and the Gata1 gene regulatory region generates a novel peroral strateg...Continue Reading

References

Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·A YoshimuraH F Lodish
Sep 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·V C BroudyJ W Adamson
Nov 12, 1993·Science·D M SpencerG R Crabtree
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·C A BlauD M Spencer
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·K OnoderaM Yamamoto
Sep 6, 2000·Nature Genetics·L JinC A Blau
Dec 18, 2002·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kinuko OhnedaMasayuki Yamamoto
Nov 16, 2005·The Journal of Biological Chemistry·Alec W Gross, Harvey F Lodish
Mar 3, 2006·The Journal of Clinical Investigation·Madhu P MenonDon M Wojchowski
Sep 20, 2006·Molecular and Cellular Biology·Stéphane PelletierJames N Ihle
Oct 13, 2006·Blood·H Franklin Bunn
Nov 14, 2007·Methods in Enzymology·Norio SuzukiMasayuki Yamamoto
Jan 8, 2008·Clinical Journal of the American Society of Nephrology : CJASN·Carol PollockEdwin Toffelmire
Mar 22, 2008·Gene Therapy·C P Miller, C A Blau
Oct 16, 2008·The Journal of Biological Chemistry·Olga BogachevaDon M Wojchowski
Oct 17, 2008·Experimental Hematology·Steve ElliottIain C Macdougall
Aug 27, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Paritha I ArumugamPunam Malik
Feb 9, 2010·The Tohoku Journal of Experimental Medicine·Kibom KimMasayuki Yamamoto
Feb 23, 2010·Current Opinion in Hematology·Don M WojchowskiArvind Dev
Sep 19, 2012·Molecular and Cellular Biology·Shin'ya OhmoriKinuko Ohneda
Mar 15, 2013·Kidney International·Toshio MiyataCharles van Ypersele de Strihou
Jul 9, 2013·Journal of the American Society of Nephrology : JASN·Tomokazu SoumaMasayuki Yamamoto
Nov 26, 2013·Transfusion Medicine and Hemotherapy : Offizielles Organ Der Deutschen Gesellschaft Fur̈ Transfusionsmedizin Und Immunham̈atologie·Wolfgang Jelkmann
Dec 7, 2013·Blood·Jeffrey W Taub

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Citations

Oct 11, 2015·Pflügers Archiv : European journal of physiology·Norio Suzuki, Masayuki Yamamoto
Sep 16, 2015·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Mario BonominiFrancesco Locatelli
Oct 4, 2015·Current Opinion in Chemical Biology·Stephanie VoßYao-Wen Wu
Aug 5, 2016·FEBS Letters·Michael S P CorbettAlan E Mark
Dec 14, 2018·Experimental and Therapeutic Medicine·Zhaoqi HuangXiming Chen

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Methods Mentioned

BETA
transgenic
myristoylation
PCR
confocal microscopy
confocal
flowcytometry

Software Mentioned

idEpoRic
Epo
CID
EpoR

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