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Conditional knockout of integrin alpha 2 beta 1 in murine megakaryocytes leads to reduced mean platelet volume

Academic Article
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Overview

authors

  • Habart, D.
  • Cheli, Y.
  • Nugent, D. J.
  • Ruggeri, Zaverio
  • Kunicki, T. J.

publication date

  • January 2013

journal

  • PLoS One  Journal

abstract

  • We have engineered a transgenic mouse on a C57BL/6 background that bears a floxed Itga2 gene. The crossing of this mouse strain to transgenic mice expressing Cre recombinase driven by the megakaryocyte (MK)-specific Pf4 promoter permits the conditional knockout of Itga2 in the MK/platelet lineage. Mice lacking MK ?2?1 develop normally, are fertile, and like their systemic ?2?1 knockout counterparts, exhibit defective adhesion to and aggregation induced by soluble type I collagen and a delayed onset to low dose fibrillar collagen-induced aggregation, results consistent with blockade or loss of platelet ?2?1. At the same time, we observed a significant reduction in mean platelet volume, which is consistent with the reported role of ?2?1 in MK maturation and proplatelet formation in vivo. This transgenic mouse strain bearing a floxed Itga2 gene will prove valuable to distinguish in vivo the temporal and spatial contributions of ?2 integrin in selected cell types.
  • We have engineered a transgenic mouse on a C57BL/6 background that bears a floxed Itga2 gene. The crossing of this mouse strain to transgenic mice expressing Cre recombinase driven by the megakaryocyte (MK)-specific Pf4 promoter permits the conditional knockout of Itga2 in the MK/platelet lineage. Mice lacking MK α2β1 develop normally, are fertile, and like their systemic α2β1 knockout counterparts, exhibit defective adhesion to and aggregation induced by soluble type I collagen and a delayed onset to low dose fibrillar collagen-induced aggregation, results consistent with blockade or loss of platelet α2β1. At the same time, we observed a significant reduction in mean platelet volume, which is consistent with the reported role of α2β1 in MK maturation and proplatelet formation in vivo. This transgenic mouse strain bearing a floxed Itga2 gene will prove valuable to distinguish in vivo the temporal and spatial contributions of α2 integrin in selected cell types.

subject areas

  • Animals
  • Base Sequence
  • Blotting, Western
  • Cell Adhesion
  • Collagen Type I
  • DNA Primers
  • Gene Knockout Techniques
  • Integrin alpha2beta1
  • Megakaryocytes
  • Mice
  • Platelet Count
  • Polymerase Chain Reaction
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Identity

PubMed Central ID

  • PMC3554675

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0055094

PubMed ID

  • 23359821
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Additional Document Info

start page

  • e55094

volume

  • 8

issue

  • 1

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