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

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

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)
180 Downloads (Pure)

Abstract

Conditional knockout (KO) mouse models are invaluable for elucidating the physiological roles of platelets. The Platelet factor 4-Cre recombinase (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 a result of 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 is 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, and dendritic and 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 as a result of nonspecific deletion in other hematopoietic lineages. By excluding leukocyte contributions to phenotypes, the Gp1ba-Cre mousewill advance our understanding of the role of platelets in inflammation and other pathophysiological processes in which platelet-leukocyte interactions are involved.

Original languageEnglish
Pages (from-to)331-343
Number of pages13
JournalBlood
Volume133
Issue number4
Early online date14 Nov 2018
DOIs
Publication statusPublished - 24 Jan 2019

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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