In vitro studies have suggested that the NMDA receptor consists of an essential subunit, NR1, and various modulatory NR2 subunits. To test this hypothesis directly in vivo, we generated mice carrying a disrupted NR1 allele. NMDA-inducible increases in intracellular calcium and membrane currents were abolished in neurons from homozygous null mutants (NR1-/-). Thus, NR1 has a unique role, which cannot be substituted by any other subunit, in determining the activity of the endogenous NMDA receptor. A concomitant reduction in levels of NR2B but not NR2A occurred in NR1-/-mice, demonstrating that there is an interdependence of subunit expression. NR1-/-mice died 8-15 hr after birth, indicating a vital neonatal function for the NMDA receptor. Although the NMDA receptor has been implicated in several aspects of neurodevelopment, overall neuroanatomy of NR1-/-mice appeared normal. Pathological evidence suggested that respiratory failure was the ultimate cause of death.
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:comment |
In vitro studies have suggested that the NMDA receptor consists of an essential subunit, NR1, and various modulatory NR2 subunits. To test this hypothesis directly in vivo, we generated mice carrying a disrupted NR1 allele. NMDA-inducible increases in intracellular calcium and membrane currents were abolished in neurons from homozygous null mutants (NR1-/-). Thus, NR1 has a unique role, which cannot be substituted by any other subunit, in determining the activity of the endogenous NMDA receptor. A concomitant reduction in levels of NR2B but not NR2A occurred in NR1-/-mice, demonstrating that there is an interdependence of subunit expression. NR1-/-mice died 8-15 hr after birth, indicating a vital neonatal function for the NMDA receptor. Although the NMDA receptor has been implicated in several aspects of neurodevelopment, overall neuroanatomy of NR1-/-mice appeared normal. Pathological evidence suggested that respiratory failure was the ultimate cause of death.
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| skos:exactMatch | |
| uniprot:name |
Neuron
|
| uniprot:author |
Connor J.A.,
Curran T.,
Forrest D.,
Luk D.C.,
Morgan J.I.,
Ng L.,
Sheng M.,
Soares H.D.,
Stewart C.L.,
Yuzaki M.
|
| uniprot:date |
1994
|
| uniprot:pages |
325-338
|
| uniprot:title |
Targeted disruption of NMDA receptor 1 gene abolishes NMDA response and results in neonatal death.
|
| uniprot:volume |
13
|
| dc-term:identifier |
doi:10.1016/0896-6273(94)90350-6
|