Skip to main content

Main menu

  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE

User menu

  • Log out
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Neuroscience
  • Log out
  • Log in
  • My Cart
Journal of Neuroscience

Advanced Search

Submit a Manuscript
  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE
PreviousNext
ARTICLE, Cellular/Molecular

Functional Consequences of Reduction in NMDA Receptor Glycine Affinity in Mice Carrying Targeted Point Mutations in the Glycine Binding Site

James N. C. Kew, Anja Koester, Jean-Luc Moreau, Francois Jenck, Abdel-Mouttalib Ouagazzal, Vincent Mutel, J. Grayson Richards, Gerhard Trube, Guenther Fischer, Alexandra Montkowski, Wolfgang Hundt, Rainer K. Reinscheid, Meike Pauly-Evers, John A. Kemp and Horst Bluethmann
Journal of Neuroscience 1 June 2000, 20 (11) 4037-4049; DOI: https://doi.org/10.1523/JNEUROSCI.20-11-04037.2000
James N. C. Kew
1Preclinical CNS Research and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anja Koester
2Roche Genetics, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Luc Moreau
1Preclinical CNS Research and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Francois Jenck
1Preclinical CNS Research and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Abdel-Mouttalib Ouagazzal
1Preclinical CNS Research and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vincent Mutel
1Preclinical CNS Research and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Grayson Richards
1Preclinical CNS Research and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gerhard Trube
1Preclinical CNS Research and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Guenther Fischer
1Preclinical CNS Research and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexandra Montkowski
3Institute of Cell Biochemistry and Clinical Neurobiology, University of Hamburg, D-22529 Hamburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wolfgang Hundt
3Institute of Cell Biochemistry and Clinical Neurobiology, University of Hamburg, D-22529 Hamburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rainer K. Reinscheid
3Institute of Cell Biochemistry and Clinical Neurobiology, University of Hamburg, D-22529 Hamburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Meike Pauly-Evers
2Roche Genetics, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John A. Kemp
1Preclinical CNS Research and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Horst Bluethmann
2Roche Genetics, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland, and
  • 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 have used site-directed mutagenesis in conjunction with homologous recombination to generate two mouse lines carrying point mutations in the glycine binding site of the NMDAR1 subunit (Grin1). Glycine concentration–response curves from acutely dissociated hippocampal neurons revealed a 5- and 86-fold reduction in receptor glycine affinity in mice carryingGrin1D481N andGrin1K483Q mutations, respectively, whereas receptor glutamate affinity remained unaffected. Homozygous mutant Grin1D481N animals are viable and fertile and appear to develop normally. However, homozygous mutant Grin1K483Q animals are significantly lighter at birth, do not feed, and die within a few days. No gross abnormalities in CNS anatomy were detected in either Grin1D481N orGrin1K483Q mice. Interestingly,in situ hybridization and Western blot analysis revealed changes in the expression levels of NMDA receptor subunits inGrin1D481N mice relative to wild type that may represent a compensatory response to the reduction in receptor glycine affinity. Grin1D481N mice exhibited deficits in hippocampal theta burst-induced long-term potentiation (LTP) and spatial learning and also a reduction in sensitivity to NMDA-induced seizures relative to wild-type controls, consistent with a reduced activation of NMDA receptors. Mutant mice exhibited normal prepulse inhibition but showed increased startle reactivity. Preliminary analysis indicated that the mice exhibit a decreased natural aversion to an exposed environment. The lethal phenotype of Grin1K483Q animals confirms the critical role of NMDA receptor activation in neonatal survival. A milder reduction in receptor glycine affinity results in an impairment of LTP and spatial learning and alterations in anxiety-related behavior, providing further evidence for the role of NMDA receptor activation in these processes.

  • NMDA receptor
  • glycine site
  • NMDAR1
  • Grin1
  • LTP
  • spatial memory
View Full Text
Back to top

In this issue

The Journal of Neuroscience: 20 (11)
Journal of Neuroscience
Vol. 20, Issue 11
1 Jun 2000
  • Table of Contents
  • Index by author
Email

Thank you for sharing this Journal of Neuroscience 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.
Functional Consequences of Reduction in NMDA Receptor Glycine Affinity in Mice Carrying Targeted Point Mutations in the Glycine Binding Site
(Your Name) has forwarded a page to you from Journal of Neuroscience
(Your Name) thought you would be interested in this article in Journal of Neuroscience.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
View Full Page PDF
Citation Tools
Functional Consequences of Reduction in NMDA Receptor Glycine Affinity in Mice Carrying Targeted Point Mutations in the Glycine Binding Site
James N. C. Kew, Anja Koester, Jean-Luc Moreau, Francois Jenck, Abdel-Mouttalib Ouagazzal, Vincent Mutel, J. Grayson Richards, Gerhard Trube, Guenther Fischer, Alexandra Montkowski, Wolfgang Hundt, Rainer K. Reinscheid, Meike Pauly-Evers, John A. Kemp, Horst Bluethmann
Journal of Neuroscience 1 June 2000, 20 (11) 4037-4049; DOI: 10.1523/JNEUROSCI.20-11-04037.2000

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Respond to this article
Request Permissions
Share
Functional Consequences of Reduction in NMDA Receptor Glycine Affinity in Mice Carrying Targeted Point Mutations in the Glycine Binding Site
James N. C. Kew, Anja Koester, Jean-Luc Moreau, Francois Jenck, Abdel-Mouttalib Ouagazzal, Vincent Mutel, J. Grayson Richards, Gerhard Trube, Guenther Fischer, Alexandra Montkowski, Wolfgang Hundt, Rainer K. Reinscheid, Meike Pauly-Evers, John A. Kemp, Horst Bluethmann
Journal of Neuroscience 1 June 2000, 20 (11) 4037-4049; DOI: 10.1523/JNEUROSCI.20-11-04037.2000
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
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • Footnotes
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Keywords

  • NMDA receptor
  • glycine site
  • NMDAR1
  • Grin1
  • LTP
  • spatial memory

Responses to this article

Respond to this article

Jump to comment:

No eLetters have been published for this article.

Related Articles

Cited By...

More in this TOC Section

ARTICLE

  • Scaffolding of Fyn Kinase to the NMDA Receptor Determines Brain Region Sensitivity to Ethanol
  • Netrin-1 Is a Chemorepellent for Oligodendrocyte Precursor Cells in the Embryonic Spinal Cord
  • Selective Enhancement of Synaptic Inhibition by Hypocretin (Orexin) in Rat Vagal Motor Neurons: Implications for Autonomic Regulation
Show more ARTICLE

Cellular/Molecular

  • Role of Voltage-Gated K+ Channels and K2P Channels in Intrinsic Electrophysiological Properties and Saltatory Conduction at Nodes of Ranvier of Rat Lumbar Spinal Ventral Nerves
  • Microglial Tmem59 Deficiency Impairs Phagocytosis of Synapse and Leads to Autism-Like Behaviors in Mice
  • Corticotropin releasing factor mediates KCa3.1 inhibition, hyperexcitability and seizures in acquired epilepsy
Show more Cellular/Molecular
  • Home
  • Alerts
  • Visit Society for Neuroscience on Facebook
  • Follow Society for Neuroscience on Twitter
  • Follow Society for Neuroscience on LinkedIn
  • Visit Society for Neuroscience on Youtube
  • Follow our RSS feeds

Content

  • Early Release
  • Current Issue
  • Issue Archive
  • Collections

Information

  • For Authors
  • For Advertisers
  • For the Media
  • For Subscribers

About

  • About the Journal
  • Editorial Board
  • Privacy Policy
  • Contact
(JNeurosci logo)
(SfN logo)

Copyright © 2022 by the Society for Neuroscience.
JNeurosci Online ISSN: 1529-2401

The ideas and opinions expressed in JNeurosci do not necessarily reflect those of SfN or the JNeurosci Editorial Board. Publication of an advertisement or other product mention in JNeurosci should not be construed as an endorsement of the manufacturer’s claims. SfN does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of any material contained in JNeurosci.