 |
 Previous Article | Next Article 
The Journal of Neuroscience, April 1, 2000, 20(7):2558-2566
Dysfunctions in Mice by NMDA Receptor Point Mutations NR1(N598Q)
and NR1(N598R)
Frank N.
Single1,
Andrei
Rozov1,
Nail
Burnashev1,
Frank
Zimmermann2,
Daniel F.
Hanley3,
Douglas
Forrest4,
Tom
Curran5,
Vidar
Jensen6,
Øivind
Hvalby6,
Rolf
Sprengel1, and
Peter H.
Seeburg1
1 Max-Planck-Institute for Medical Research,
Departments of Molecular Neuroscience and Cell Physiology, Jahnstra e
29, D-69120 Heidelberg, Germany, 2 Center for Molecular
Biology, University of Heidelberg, D-69120 Heidelberg, Germany,
3 Johns Hopkins School of Medicine, Department of
Neurology, Baltimore, Maryland 21287-7840, 4 Mount Sinai
School of Medicine, Department of Human Genetics, New York, New York
10029, 5 St. Jude Children's Research Hospital, Department
of Developmental Neurobiology, Memphis, Tennessee 38105, and
6 Institute of Basic Medical Sciences, Department of
Neurophysiology, University of Oslo, Blindern, N-0317 Oslo, Norway
NMDA receptors in mice were mutated by gene targeting to substitute
asparagine (N) in position 598 of the NR1 subunit to glutamine (Q) or
arginine (R). Animals expressing exclusively the mutated NR1 alleles, NR1Q/Q and
NR1 /R mice, developed a perinatally lethal
phenotype mainly characterized by respiratory failure. The dysfunctions
were partially rescued in heterozygous mice by the presence of pure
wild-type receptors. Thus, NR1+/Q mice
exhibited reduced life expectancy, with females being impaired in
nurturing; NR1+/R mice displayed signs of
underdevelopment such as growth retardation and impaired righting
reflex, and died before weaning. We analyzed the key properties of NMDA
receptors, high Ca2+ permeability, and
voltage-dependent Mg2+ block, in the mutant mice.
Comparison of the complex physiological and phenotypical changes
observed in the different mutants indicates that properties controlled
by NR1 subunit residue N598 are important for autonomic brain functions
at birth and during postnatal development. We conclude that disturbed
NMDA receptor signaling mediates a variety of neurological phenotypes.
Key words:
NMDA receptor; gene targeting; Cre-loxP; Mg2+ block; Ca2+ influx; coincidence detection; respiration; nurturing; barrel cortex; LTP
Copyright © 2000 Society for Neuroscience 0270-6474/00/2072558-09$05.00/0
This article has been cited by other articles:
|
|
|
|
 
F.-S. Lo and R. S. Erzurumlu
Conversion of Functional Synapses into Silent Synapses in the Trigeminal Brainstem after Neonatal Peripheral Nerve Transection
J. Neurosci.,
May 2, 2007;
27(18):
4929 - 4934.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. K. Friedman
CALCIUM: A Role for Neuroprotection and Sustained Adaptation
Mol. Interv.,
December 1, 2006;
6(6):
315 - 329.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. C. Gammie
Current Models and Future Directions for Understanding the Neural Circuitries of Maternal Behaviors in Rodents
Behav Cogn Neurosci Rev,
June 1, 2005;
4(2):
119 - 135.
[Abstract]
[PDF]
|
|
|
|
|
|
|
V. Pawlak, B. J Schupp, F. N Single, P. H Seeburg, and G. Kohr
Impaired synaptic scaling in mouse hippocampal neurones expressing NMDA receptors with reduced calcium permeability
J. Physiol.,
February 1, 2005;
562(3):
771 - 783.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Simeone, R. M. Sanchez, and J. M. Rho
Molecular Biology and Ontogeny of Glutamate Receptors in the Mammalian Central Nervous System
J Child Neurol,
May 1, 2004;
19(5):
343 - 360.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K. Jensen, C.-S. Chiu, I. Sokolova, H. A. Lester, and I. Mody
GABA Transporter-1 (GAT1)-Deficient Mice: Differential Tonic Activation of GABAA Versus GABAB Receptors in the Hippocampus
J Neurophysiol,
October 1, 2003;
90(4):
2690 - 2701.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Fonck, R. Nashmi, P. Deshpande, M. I. Damaj, M. J. Marks, A. Riedel, J. Schwarz, A. C. Collins, C. Labarca, and H. A. Lester
Increased Sensitivity to Agonist-Induced Seizures, Straub Tail, and Hippocampal Theta Rhythm in Knock-In Mice Carrying Hypersensitive alpha 4 Nicotinic Receptors
J. Neurosci.,
April 1, 2003;
23(7):
2582 - 2590.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Rudhard, M. Kneussel, M. A. Nassar, G. F. Rast, A. J. Annala, P. E. Chen, C. M. Tigaret, I. Dean, J. Roes, A. J. Gibb, et al.
Absence of Whisker-Related Pattern Formation in Mice with NMDA Receptors Lacking Coincidence Detection Properties and Calcium Signaling
J. Neurosci.,
March 15, 2003;
23(6):
2323 - 2332.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Y. Vekovischeva, D. Zamanillo, O. Echenko, T. Seppala, M. Uusi-Oukari, A. Honkanen, P. H. Seeburg, R. Sprengel, and E. R. Korpi
Morphine-Induced Dependence and Sensitization Are Altered in Mice Deficient in AMPA-Type Glutamate Receptor-A Subunits
J. Neurosci.,
June 15, 2001;
21(12):
4451 - 4459.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Labarca, J. Schwarz, P. Deshpande, S. Schwarz, M. W. Nowak, C. Fonck, R. Nashmi, P. Kofuji, H. Dang, W. Shi, et al.
Point mutant mice with hypersensitive alpha 4 nicotinic receptors show dopaminergic deficits and increased anxiety
PNAS,
February 15, 2001;
(2001)
41582598.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
N. Sugiura, R. G. Patel, and R. A. Corriveau
N-Methyl-D-aspartate Receptors Regulate a Group of Transiently Expressed Genes in the Developing Brain
J. Biol. Chem.,
April 20, 2001;
276(17):
14257 - 14263.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Labarca, J. Schwarz, P. Deshpande, S. Schwarz, M. W. Nowak, C. Fonck, R. Nashmi, P. Kofuji, H. Dang, W. Shi, et al.
Point mutant mice with hypersensitive alpha 4 nicotinic receptors show dopaminergic deficits and increased anxiety
PNAS,
February 27, 2001;
98(5):
2786 - 2791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
