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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1503-1506.
Prepublished online as a Blood First Edition Paper on October 10, 2006; DOI 10.1182/blood-2006-04-020362.


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Submitted April 28, 2006
Accepted September 26, 2006

Pf4-Cre transgenic mice allow generating lineage-restricted gene knockouts for studying megakaryocyte and platelet function in vivo

Ralph Tiedt, Tibor Schomber, Hui Hao-Shen, and Radek C Skoda*

Department of Research, Experimental Hematology, University Hospital Basel, Basel, Switzerland

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

To generate transgenic mice that express Cre-recombinase exclusively in the megakaryocytic lineage, we modified a mouse bacterial artificial chromosome (BAC) clone by homologous recombination and replaced the first exon of the platelet factor 4 (Pf4), also called CXCL4, with a codon-improved Cre cDNA. Several strains expressing the transgene were obtained and one strain, Q3, was studied in detail. Crossing Q3 mice with the ROSA26-lacZ reporter strain showed that Cre-recombinase activity was confined to megakaryocytes. These results were further verified by crossing the Q3 mice with a strain containing loxP-flanked integrin {beta}1. Excision of this conditional allele in megakaryocytes was complete at the DNA level and platelets were virtually devoid of the integrin {beta}1 protein. The Pf4-Cre transgenic strain will be a valuable tool to study megakaryopoiesis, platelet formation and platelet function.


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