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The Gp1ba-Cre transgenic mouse: a new model to delineate platelet and leukocyte functions

Zoltan Nagy, Timo Vögtle, Mitchell J. Geer, Jun Mori, Silke Heising, Giada Di Nunzio, Ralph Gareus, Alexander Tarakhovsky, Arthur Weiss, Benjamin G. Neel, Guillaume E. Desanti, Alexandra Mazharian and Yotis A. Senis

Key points

  • The Gp1ba-Cre mouse allows highly specific deletion of floxed genes in the megakaryocyte lineage.

  • The Gp1ba-Cre mouse enables differentiation of platelet and leukocyte functions.

Abstract

Conditional knockout (KO) mouse models are invaluable for elucidating the physiological roles of platelets. The Pf4-Cre transgenic mouse is the current model of choice for generating megakaryocyte/platelet-specific KO mice. Platelets and leukocytes work closely together in a wide range of disease settings, yet the specific contribution of platelets to these processes remains unclear. This is partially due to the Pf4-Cre transgene being expressed in a variety of leukocyte populations. To overcome this issue, we developed a Gp1ba-Cre transgenic mouse strain in which Cre expression in driven by the endogenous Gp1ba locus. By crossing Gp1ba-Cre and Pf4-Cre mice to the mT/mG dual-fluorescence reporter mouse and performing a head-to-head comparison, we demonstrate more stringent megakaryocyte lineage-specific expression of the Gp1ba-Cre transgene. Broader tissue expression was observed with the Pf4-Cre transgene, leading to recombination in many hematopoietic lineages, including monocytes, macrophages, granulocytes, dendritic, B and T cells. Direct comparison of phenotypes of Csk, Shp1 or CD148 conditional KO mice generated using either the Gp1ba-Cre or Pf4-Cre strains revealed similar platelet phenotypes. However, additional inflammatory and immunological anomalies were observed in Pf4-Cre-generated KO mice due to non-specific deletion in other hematopoietic lineages. By excluding leukocyte contributions to phenotypes, the Gp1ba-Cre mouse will advance our understanding of the role of platelets in inflammation and other pathophysiological processes where platelet-leukocyte interactions are involved.

  • Submitted September 28, 2018.
  • Accepted October 26, 2018.