Broader expression of the mouse Platelet Factor 4-Cre transgene beyond the megakaryocyte lineage.
Fiche publication
Date publication
novembre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DULUC Isabelle, Dr FREUND Jean-Noël
Tous les auteurs :
Pertuy F, Aguilar A, Strassel C, Eckly A, Freund JN, Duluc I, Gachet C, Lanza F, Leon C
Lien Pubmed
Résumé
BACKGROUND: Transgenic mice expressing cre recombinase under the control of the Platelet Factor 4 (Pf4) promoter, in the context of 100 kb bacterial artificial chromosome, have become a valuable tool to study genetic modifications in the platelet lineage. However, the specificity of cre expression has recently been questioned and the time of its onset during megakaryopoiesis remains unknown. Objectives/ METHODS: To characterize the expression of this transgene, we used double fluorescent cre-reporter mice. RESULTS: In the bone marrow, Pf4-cre-mediated recombination had occurred in all CD42-positive megakaryocytes, as early as stage I of maturation, and in rare CD42-negative cells. In circulating blood, all platelets had recombined, along with only a minor fraction of CD45-positive cells. However we show that all tissues contain recombined cells of monocyte/macrophage origin. When recombined, these cells might potentially modify the function of the tissues under particular conditions, especially inflammatory ones which further increases the recombination in immune cells. Unexpectedly, a subset of epithelial cells from the distal colon showed signs of recombination due to endogenous Pf4-cre expression. This is probably at the origin of unexplained colon tumors developed by Apcflox/flox ;Pf4-cre mice, generated in a separate study on the role of Apc in platelet formation. CONCLUSION: Altogether, our results indicate early recombination with full penetrance in megakaryopoiesis and confirm the value of Pf4-cre mice for the genetic engineering of megakaryocytes and platelets. However, care must be taken when investigating the role of platelets in processes outside hemostasis, especially when immune cells might be involved. This article is protected by copyright. All rights reserved.
Référence
J Thromb Haemost. 2014 Nov 13