title: Pf4-Cre transgenic mice allow the generation of lineage-restricted gene knockouts for studying megakaryocyte and platelet function in vivo.
abstract: 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 beta1. Excision of this conditional allele in megakaryocytes was complete at the DNA level, and platelets were virtually devoid of the integrin beta1 protein. The Pf4-Cre transgenic strain will be a valuable tool to study megakaryopoiesis, platelet formation, and platelet function.
authors.affiliation: Department of Research and Experimental Hematology, University Hospital Basel, Switzerland.
authors.forename: Ralph
authors.initials: R
authors.lastname: Tiedt
authors.forename: Tibor
authors.initials: T
authors.lastname: Schomber
authors.forename: Hui
authors.initials: H
authors.lastname: Hao-Shen
authors.forename: Radek C
authors.initials: RC
authors.lastname: Skoda
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D019070:Cell Lineage; D022202:Chromosomes, Artificial, Bacterial; D019426:Integrases / Q000032:analysis / Q000235:genetics; D008533:Megakaryocytes / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010978:Platelet Factor 4 / Q000235:genetics*; D011995:Recombination, Genetic; D019076:Transgenes
chemical_list: D010978:Platelet Factor 4; C045073:Cre recombinase; D019426:Integrases