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Prepublished online as a Blood First Edition Paper on June 28, 2002; DOI 10.1182/blood-2002-01-0281.

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Submitted January 30, 2002
Accepted March 21, 2002

A 2 kb c-mpl promoter fragment is sufficient to direct expression to the megakaryocytic lineage and sites of embryonic hematopoiesis in transgenic mice

Sandra Ziegler, Kurt Burki, and Radek C Skoda*

Biozentrum, University of Basel, Basel, Switzerland
Institute for Laboratory Animal Sciences, University of Zurich, Zurich, Switzerland
Biozentrum, University of Basel, Basel, Switzerland; German Cancer research Center (DKFZ), Heidelberg, Germany

* Corresponding author; email: radek.skoda{at}unibas.ch.

The thrombopoietin receptor, c-mpl, is expressed on hematopoietic progenitors and cells of the megakaryocytic lineage. The c-mpl promoter may therefore be very useful for directing expression of transgenes. We tested whether a 2 kb genomic DNA fragment comprising the putative c-mpl regulatory elements and most of the 5'-untranslated region of mouse c-mpl is able to direct expression of a reporter gene to hematopoietic cells in transgenic mice. As a reporter gene we used the human placental alkaline phosphatase (PLAP). In adult transgenic mice, PLAP expression was specifically detected in megakaryocytes and platelets. Embryos showed PLAP reporter gene expression already in the yolk sac at embryonic day 6.5 (E6.5) and in blood islands at E7.5. At E9.5 expression was found in blood vessels of the yolk sac and the embryo proper followed by high levels of expression in the fetal liver at E11.5. Expression in E6.5 yolk sac is compatible with a function of c-mpl and its ligand TPO in the earliest stages of embryonic hematopoiesis.


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