Regulated Human Erythropoietin Receptor Expression in Mouse Brain*
- From the Laboratory of Chemical Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1822
Abstract
Erythropoietin (Epo) is known for its role in erythropoiesis and acts by binding to its receptor (EpoR) on the surface of erythroid progenitors. EpoR activity follows the site of hematopoiesis from the embryonic yolk sac to the fetal liver and then the adult spleen and bone marrow. Expression of EpoR has also been observed in selected cells of non-hematopoietic origin, such as the embryonic mouse brain during mid-gestation, at levels comparable to adult bone marrow. EpoR transcripts in brain decrease during development falling by birth to less than 1–3% of the level in hematopoietic tissue. We have now recapitulated this pattern of expression using a human EpoR transgene consisting of an 80-kb human EpoR genomic fragment. The highest level of expression was observed in the embryonic yolk sac and fetal liver, analogous to the endogenous gene, in addition to expression in adult spleen and bone marrow. Although activity of this transgene in brain is initially lower than the endogenous gene, it does exhibit the down-regulation observed for the endogenous gene in adult brain. The expression pattern of hybrid transgenes of an hEpoR promoter fused to β-galactosidase in 9.5-day embryos suggested that the hEpoR promoter region between −1778 and −150 bp 5′ of the transcription start site is necessary to direct EpoR expression in the neural tube. EpoR expression in the neural tube may be the origin of the EpoR transcripts detected in brain during development. These data demonstrate that both the mouse and human EpoR genes contain regulatory elements to direct significant levels of expression in a developmentally controlled manner in brain and suggest that in addition to its function during erythropoiesis, EpoR may play a role in the development of selected non-hematopoietic tissue.
Footnotes
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed. Tel.: 301-496-1164; Fax: 301-402-0101; E-mail: cnoguchi{at}helix.nih.gov.
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↵1 The abbreviations used are: Epo, erythropoietin; EpoR, erythropoietin receptor; hEpoR, human erythropoietin receptor; mEpoR, mouse erythropoietin receptor; kb, kilobase(s); bp, base pair(s); PCR, polymerase chain reaction; RT, reverse transcriptase.
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- Received July 14, 1997.
- Revision received October 7, 1997.
