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The Modifier of hemostasis (Mh) locus on chromosome 4 controls in vivo hemostasis of Gp6(-/-) mice

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Overview

authors

  • Cheli, Y.
  • Jensen, D.
  • Marchese, P.
  • Habart, D.
  • Wiltshire, T.
  • Cooke, M.
  • Fernandez, J. A.
  • Ware, J.
  • Ruggeri, Zaverio
  • Kunicki, T. J.

publication date

  • February 2008

journal

  • Blood  Journal

abstract

  • Platelet glycoprotein VI (GPVI) is a key receptor for collagens that mediates the propagation of platelet attachment and activation. Targeted disruption of the murine gene Gp6 on a mixed 129 x 1/SvJ x C57BL/6J background causes the expected defects in collagen-dependent platelet responses in vitro. The extent of this dysfunction in all Gp6(-/-) mice is uniform and is not affected by genetic background. However, the same Gp6(-/-) mice exhibit 2 diametrically opposed phenotypes in vivo. In some mice, tail bleeding times are extremely prolonged, and thrombus formation in an in vivo carotid artery ferric chloride-injury model is significantly impaired. In other littermates, tail bleeding times are within the range of wild-type mice, and in vivo thrombus formation is indistinguishable from that of control mice. Directed intercrosses revealed that these phenotypes are heritable, and a genome-wide single-nucleotide polymorphism scan revealed the most significant linkage to a single locus (8 megabases) on chromosome 4 (logarithm of the odds [LOD] score = 6.9, P < .0001) that we designate Modifier of hemostasis (Mh). Our results indicate that one or more modifier genes in Mh control the extent to which in vivo platelet thrombus formation is disrupted by the absence of platelet GPVI.

subject areas

  • Animals
  • Arteries
  • Bleeding Time
  • Blood Coagulation
  • Blood Platelets
  • Cell Membrane
  • Chromosomes
  • Genome
  • Hemostasis
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Platelet Aggregation
  • Platelet Membrane Glycoproteins
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Identity

PubMed Central ID

  • PMC2214743

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2007-09-111369

PubMed ID

  • 17991808
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Additional Document Info

start page

  • 1266

end page

  • 1273

volume

  • 111

issue

  • 3

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