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
Molecular Pharmacology
  • 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
Molecular Pharmacology

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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Humanization of Mouse 5-Hydroxytryptamine1B Receptor Gene by Homologous Recombination: In Vitro and In Vivo Characterization

P. Bonaventure, L. Umans, M. H. M. Bakker, P. Cras, X. Langlois, W. H. M. L. Luyten, A. A. H. P. Megens, L. Serneels, F. Van Leuven and J. E. Leysen
Molecular Pharmacology July 1999, 56 (1) 54-67; DOI: https://doi.org/10.1124/mol.56.1.54
P. Bonaventure
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L. Umans
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. H. M. Bakker
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P. Cras
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
X. Langlois
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
W. H. M. L. Luyten
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A. A. H. P. Megens
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L. Serneels
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
F. Van Leuven
1 2 3 4 5 6
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. E. Leysen
1 2 3 4 5 6
  • 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
Loading

Abstract

We replaced the coding region of the murine 5-hydroxytryptamine (5-HT)1B receptor by the human 5-HT1B receptor using homologous recombination in embryonic stem cells and generated and characterized homozygous transgenic mice that express only the human (h) 5-HT1B receptor. The distribution patterns of h5-HT1B and murine (m) 5-HT1B receptor mRNA and binding sites in brain sections of transgenic and wild-type mice were identical as measured by in situ hybridization histochemistry and radioligand receptor autoradiography. When measured in parallel under identical conditions, the h5-HT1B receptor expressed in mouse brain had the same pharmacological characteristics as that in human brain. Stimulation by 5-HT1B agonists of [35S]guanosine-5′-O-(3-thio)triphosphate binding in brain sections demonstrated the functional coupling of the h5-HT1B receptor to G proteins in mouse brain. In tissue slices from various brain regions, electrically stimulated [3H]5-HT release was not modified by 5-HT1Bagonists in tissue from either transgenic and wild-type mice; a 5-HT1B antagonist enhanced electrically stimulated [3H]5-HT release in wild-type mouse brain, but was ineffective in the transgenics. The centrally active 5-HT1A/5-HT1B agonist RU24969 induced hypothermia but did not increase locomotor activity in the transgenic mice. The ineffectiveness of RU24969 in the transgenic mice could be due to the lower affinity of the compound for the h5-HT1Breceptor compared with the m5-HT1B receptor. The present study demonstrates a complete replacement of the mouse receptor by its human receptor homolog and a functional coupling to G proteins. However, modulation of [3H]5-HT release could not be shown. Furthermore, behavioral effects were not clearly observed, which may be due to a lack of appropriate tools.

Footnotes

    • Received January 26, 1999.
    • Accepted March 21, 1999.
  • Send reprint requests to: Dr. Pascal Bonaventure, R.W. Johnson Pharmaceutical Research Institute, 3535 General Atomic Court, Suite 100, San Diego, CA. E-mail: pbonave1{at}prius.jnj.com

  • ↵1 These two authors contributed equally to this work.

  • ↵2 Current address: R. W. Johnson Pharmaceutical Research Institute, 3535 General Atomic Court, Suite 100, San Diego, CA 92122.

  • The experimental Genetics Group, Centrum voor Menselijke Erfelijkheid, Vlaams Interuniversitair Instituut voor Biotechnologie, Katholieke Universiteit Leuven was supported by grants from FWO-Vlaanderen, the Interuniversity Attraction Pole program (IUAP) of the Belgian government, and the Biotechnology Program of the Flemish government (IWT/VLAB/COT-008). L.U. was a postdoctoral research fellow of the Katholieke Universiteit Leuven Research Fund.

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm 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

Molecular Pharmacology: 56 (1)
Molecular Pharmacology
Vol. 56, Issue 1
1 Jul 1999
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology 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.
Humanization of Mouse 5-Hydroxytryptamine1B Receptor Gene by Homologous Recombination: In Vitro and In Vivo Characterization
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Humanization of Mouse 5-Hydroxytryptamine1B Receptor Gene by Homologous Recombination: In Vitro and In Vivo Characterization

P. Bonaventure, L. Umans, M. H. M. Bakker, P. Cras, X. Langlois, W. H. M. L. Luyten, A. A. H. P. Megens, L. Serneels, F. Van Leuven and J. E. Leysen
Molecular Pharmacology July 1, 1999, 56 (1) 54-67; DOI: https://doi.org/10.1124/mol.56.1.54

Citation Manager Formats

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

Humanization of Mouse 5-Hydroxytryptamine1B Receptor Gene by Homologous Recombination: In Vitro and In Vivo Characterization

P. Bonaventure, L. Umans, M. H. M. Bakker, P. Cras, X. Langlois, W. H. M. L. Luyten, A. A. H. P. Megens, L. Serneels, F. Van Leuven and J. E. Leysen
Molecular Pharmacology July 1, 1999, 56 (1) 54-67; DOI: https://doi.org/10.1124/mol.56.1.54
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
    • Experimental Procedures
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • 6-Methylflavone Blocks Bitterness of Tenofovir
  • Positive Allosteric Modulation of the mGlu5 Receptor
  • Correction of mutant CNGA3 channel trafficking defect
Show more Article

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 Molecular Pharmacology
  • 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
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

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