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
1. Excision of this conditional allele in megakaryocytes was complete at the DNA level and platelets were virtually devoid of the integrin
1 protein. The Pf4-Cre transgenic strain will be a valuable tool to study megakaryopoiesis, platelet formation and platelet function.