Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleCardiovascular

A Humanized Glycoprotein VI (GPVI) Mouse Model to Assess the Antithrombotic Efficacies of Anti-GPVI Agents

Pierre Henri Mangin, ChaoJun Tang, Catherine Bourdon, Stéphane Loyau, Monique Freund, Béatrice Hechler, Christian Gachet and Martine Jandrot-Perrus
Journal of Pharmacology and Experimental Therapeutics April 2012, 341 (1) 156-163; DOI: https://doi.org/10.1124/jpet.111.189050
Pierre Henri Mangin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
ChaoJun Tang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Catherine Bourdon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stéphane Loyau
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Monique Freund
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Béatrice Hechler
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christian Gachet
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martine Jandrot-Perrus
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

Abstract

Glycoprotein VI (GPVI) has been proposed as a promising antiplatelet target, because its blockade prevents experimental thrombosis without impairing hemostasis. The objective of this study was to develop a preclinical tool to evaluate the role of human GPVI (hGPVI) in various models of thrombosis and to screen anti-GPVI compounds. A genetically modified mouse strain expressing hGPVI has been developed using a knockin strategy. The mice were viable and fertile and did not present any hematological defects. Approximately 3700 copies of human GPVI were detected at the platelet surface. Platelet aggregation, fibrinogen binding, and P-selectin exposure were normal in response to various agonists. The 9O12.2 Fab fragment directed against human GPVI bound to hGPVI platelets in vitro and ex vivo and markedly reduced collagen- and collagen-related peptide-induced responses. Injection of 9O12.2 into hGPVI animals did not prolong the tail bleeding time but provided protection against lethal thromboembolism induced by a collagen/adrenaline mixture. In addition, 9O12.2 reduced arterial thrombus growth by 44% after superficial laser injury, 43% after deep laser injury in mice pretreated with hirudin, and 48% after mechanical injury. In conclusion, we have developed a humanized mouse model that could be used in preclinical studies to evaluate the effects of anti-GPVI compounds.

Footnotes

  • This work was supported by the Institut National de la Santé et de la Recherche Médicale, the Fondation de France [Grant 2007001960]; the Agence National de la Recherche [Grant 07EPMB-002-01]; and the Seventh Framework Programme of the European Comission [Grant 260309]. C.T. is supported by postdoctoral fellowship from the French Chinese Foundation for Science and Applications.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    http://dx.doi.org/10.1124/jpet.111.189050.

  • ↵Embedded Image The online version of this article (available at http://jpet.aspetjournals.org) contains supplemental material.

  • ABBREVIATIONS:

    GPVI
    glycoprotein VI
    ApoE
    apolipoprotein E
    CRP
    collagen-related peptide
    DIOC6
    3,3′-dihexyloxacarbocyanine iodide
    ES
    embryonic stem
    FITC
    fluorescein isothiocyanate
    hGPVI
    human glycoprotein VI
    MFI
    mean fluorescence intensity
    mGPVI
    mouse glycoprotein VI
    PCR
    polymerase chain reaction
    WT
    wild-type
    SV40
    simian virus 40.

  • Received October 14, 2011.
  • Accepted January 9, 2012.
  • Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 341 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 341, Issue 1
1 Apr 2012
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
A Humanized Glycoprotein VI (GPVI) Mouse Model to Assess the Antithrombotic Efficacies of Anti-GPVI Agents
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleCardiovascular

Humanized GPVI Mouse Model

Pierre Henri Mangin, ChaoJun Tang, Catherine Bourdon, Stéphane Loyau, Monique Freund, Béatrice Hechler, Christian Gachet and Martine Jandrot-Perrus
Journal of Pharmacology and Experimental Therapeutics April 1, 2012, 341 (1) 156-163; DOI: https://doi.org/10.1124/jpet.111.189050

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleCardiovascular

Humanized GPVI Mouse Model

Pierre Henri Mangin, ChaoJun Tang, Catherine Bourdon, Stéphane Loyau, Monique Freund, Béatrice Hechler, Christian Gachet and Martine Jandrot-Perrus
Journal of Pharmacology and Experimental Therapeutics April 1, 2012, 341 (1) 156-163; DOI: https://doi.org/10.1124/jpet.111.189050
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Improved Assessment of Cardiovascular Safety Data
  • G6PD, DNA methylation, and PAH
  • Effect of Acetate on HR, Blood Pressure, and Cardiac Contractility
Show more Cardiovascular

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics