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Volume 272, Number 51, Issue of December 19, 1997
pp. 32395-32400
(Received for publication, July 14, 1997, and in revised form, October 7, 1997)
From the Laboratory of Chemical Biology, NIDDK, National Institutes
of Health, Bethesda, Maryland 20892-1822
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
Regulated Human Erythropoietin Receptor Expression in Mouse
Brain
-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.
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